Готові списки джерел за темами / Monoclonal antibody, immunocytokine, immunotherapy

Зміст

Статті в журналах
Дисертації
Книги
Частини книг
Тези доповідей конференцій

Добірка наукової літератури з теми "Monoclonal antibody, immunocytokine, immunotherapy"

Автор: Grafiati

Опубліковано: 11 березня 2023

Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями

Оберіть тип джерела:

Ознайомтеся зі списками актуальних статей, книг, дисертацій, тез та інших наукових джерел на тему "Monoclonal antibody, immunocytokine, immunotherapy".

Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.

Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.

Статті в журналах з теми "Monoclonal antibody, immunocytokine, immunotherapy"

Singh, Harjeet, Lisa Marie A. Serrano, Simon Olivares, Michael Jensen, George McNamara, David Colcher, Andrew Raubitschek, and Laurence J. N. Cooper. "Combining Immunocytokine with Adoptive Immunotherapy To Treat B-Lineage Lymphomas." Blood 106, no. 11 (November 16, 2005): 343. http://dx.doi.org/10.1182/blood.v106.11.343.343.

Повний текст джерела

Анотація:

Abstract Lineage-specific cell-surface molecules, such as CD19 and CD20 on B-lineage malignancies are the targets for immunotherapies. However, the therapeutic success of CD19-specific T-cell therapy is predicted to be dependent on the continued persistence of adoptively transferred T cells. It is well-recognized that exogenous IL-2 can help sustain the in vivo persistence of ex vivo-propagated CD8+ T cells. Therefore, in order to target biologically active IL-2 to the tumor microenvironment, we have used an immunocytokine (ICK) to deliver this cytokine to binding-sites of a CD20-specific monoclonal antibody (mAb) on malignant B cells. This anti-CD20-IL2 ICK was based on the Leu16 anti-CD20 mAb that was dehumanized to remove T-helper epitopes. Flow cytometry demonstrated that anti-CD20-IL2 ICK specifically bound to CD20+ tumor and IL-2R+ T cells. Thus, we investigated the ability of this ICK to improve the persistence of adoptively transferred B-lineage lymphoma-specific T cells. To obtain CD19-specific T cells that could be non-invasively imaged in vivo, we used non-viral gene transfer to introduce a DNA plasmid to co-express both a CD19-specific immunoreceptor (designated CD19R) and firefly luciferase (ffLuc). The CD19R combines antibody recognition with T-cell effector functions mediated through CD3-ζ . The genetically modified T cells were characterized as differentiated CD8+ effector cells expressing the IL-2 receptor complex, which specifically recognize and lyse CD19+ lymphoma targets. To model the survival of adoptively transferred T cells and treatment of lymphoma in vivo, we generated a CD20+CD19+ ARH-77 tumor line expressing the Renilla luciferase (rLuc) reporter gene. Our data demonstrate that this tumor line is resistant to a CD20-specific mAb, Rituximab, in vivo. Sub-optimal doses of CD19R+ffLuc+ CD8+ T cells, which do not cause complete eradication of tumor by themselves, were infused along with anti-CD20-IL2 ICK and control ICK (with irrelevant specificity) in NOD/scid mice bearing xenografts of the rLuc+ tumor. In vivo non-invasive bioluminescent imaging (BLI) was used to longitudinally measure the persistence of ffluc+ T cells and growth of rluc+ tumor. In our mouse model, the T cells persisted significantly (p<0.05) longer in the mice treated with anti-CD20-IL2 ICK, compared to mice receiving the ICK with an irrelevant specificity. This improvement in T-cell persistence translated into augmented anti-tumor activity (Figure). These results suggest that combining tumor-specific ICK with tumor-specific T cells may improve the outcome of immunotherapy. Since Phase I trials are underway using anti-CD20-IL2 ICK and CD19-specific T cells as monotherapy, our results warrant clinical trials using combination of these immunotherapies. Synergistic anti-tumor effect of tumor-specific ICK and tumor-specific T cells. Serial pseudo-color images represent light intensity from rluc(+) ARH-77 cells in NOD/scid mice before and after immunotherapies. The irrelevant immunocytokine has specificity for GD2 which is not expressed on tumor cells. Synergistic anti-tumor effect of tumor-specific ICK and tumor-specific T cells. Serial pseudo-color images represent light intensity from rluc(+) ARH-77 cells in NOD/scid mice before and after immunotherapies. The irrelevant immunocytokine has specificity for GD2 which is not expressed on tumor cells.

Стилі APA, Harvard, Vancouver, ISO та ін.

Aiken, Taylor, Julie Voeller, Amy Erbe, Alexander Rakhmilevich, and Paul Sondel. "458 Antitumor mechanisms of local radiation and combination immunotherapy in an immunologically cold model of neuroblastoma." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (November 2020): A486. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0458.

Повний текст джерела

Анотація:

BackgroundThe standard treatment for high-risk neuroblastoma includes a combination immunotherapeutic approach consisting of IL-2, GM-CSF, and monoclonal antibodies directed against GD2, a disialoganglioside preferentially expressed in neuroblastoma and melanoma (1). We recently described an effective a preclinical in-situ vaccination strategy combining local radiation therapy (RT), IL-2-linked to anti-GD2 monoclonal antibody (intratumoral immunocytokine, IT-IC), checkpoint inhibition (anti-CTLA4), and drivers of innate immunity (anti-CD40 and CpG) (2). This strategy is effective in curing mice with immunologically-cold neuroblastoma. We sought to better characterize the anti-tumor mechanisms that mediate this effect.MethodsMice bearing GD2-expressing, immunologically-cold neuroblastoma tumors (9464D-GD2) were treated with 12Gy RT and combination immunotherapy (IT-IC, anti-CTLA-4, CpG, anti-CD40) over 12 days as previously described (2). Depletion of individual immune cell sets during treatment was achieved by depleting monoclonal antibodies and confirmed by flow cytometry. T-cell receptor deficient (TCR KO) mice were used to confirm findings in T-cell depletion experiments. 9464D-GD2 parental cells have low MHC-I expression; subclones with low and moderate MHC Class I expression were obtained by flow cytometry sorting and the impact of MHC class I expression on immune cell infiltrate and survival was assessed.ResultsThe effectiveness of RT and combination immunotherapy was not significantly reduced by NK or T cell depletion, and TCR KO mice had similar tumor growth and survival to mice that underwent T-cell depletion. Moderate MHC class I expression did not slow tumor growth or improve survival in mice bearing 9464D-GD2 tumors (over those with low MHC-I) following treatment. Moderate MHC class I expression also did not alter individual immune cell subsets in treated tumors. Overall, increased infiltration of CD8 T-cells, CD4 T-cells, and depletion of T regulatory cells was observed in all treated tumors (p<0.05).Abstract 458 Figure 1Effect of MHC class I expression on response to RT and combination immunotherapy (IT-IC, anti-CTLA4, anti-CD40, CpG). A) Increased MHC class I expression in 9464D-GD2 derived tumors did not alter tumor growth or survival following treatment. B) Increased MHC class I expression did not alter immune subsets following treatment of 9464D-GD tumors with radiation and combination immunotherapy. Increased numbers of CD8+ and CD4+ T-cells was observed with both moderate and absent MHC class I expression. T regulatory cells were also effectively depleted in both treated groupsConclusionsTreatment with RT and combination immunotherapy (IT-IC, anti-CTLA4, anti-CD40, CpG) may act through mechanisms that are MHC class I, NK-cell and T-cell independent. Further investigation of the role of innate immunity and myeloid subsets in this scenario is warranted.AcknowledgementsResearch reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number T32 CA090217.ReferencesYu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, et al. Anti-GD2 Antibody with GM-CSF, Interleukin-2, and Isotretinoin for Neuroblastoma. New England Journal of Medicine 2010;363:1324–34Voeller J, Erbe AK, Slowinski J, Rasmussen K, Carlson PM, Hoefges A, et al. Combined innate and adaptive immunotherapy overcomes resistance of immunologically cold syngeneic murine neuroblastoma to checkpoint inhibition. Journal for Immunotherapy of Cancer 2019;7:13

Стилі APA, Harvard, Vancouver, ISO та ін.

Alderson, Kory L., and Paul M. Sondel. "Clinical Cancer Therapy by NK Cells via Antibody-Dependent Cell-Mediated Cytotoxicity." Journal of Biomedicine and Biotechnology 2011 (2011): 1–7. http://dx.doi.org/10.1155/2011/379123.

Повний текст джерела

Анотація:

Natural killer (NK) cells are powerful effector cells that can be directed to eliminate tumor cells through tumor-targeted monoclonal antibodies (mAbs). Some tumor-targeted mAbs have been successfully applied in the clinic and are included in the standard of care for certain malignancies. Strategies to augment the antitumor response by NK cells have led to an increased understanding of how to improve their effector responses. Next-generation reagents, such as molecularly modified mAbs and mAb-cytokine fusion proteins (immunocytokines, ICs) designed to augment NK-mediated killing, are showing promise in preclinical and some clinical settings. Continued research into the antitumor effects induced by NK cells and tumor-targeted mAbs suggests that additional intrinsic and extrinsic factors may influence the antitumor response. Therefore more research is needed that focuses on evaluating which NK cell and tumor criteria are best predictive of a clinical response and which combination immunotherapy regimens to pursue for distinct clinical settings.

Стилі APA, Harvard, Vancouver, ISO та ін.

Aiken, Taylor J., David Komjathy, Mat Rodriguez, Arika Feils, Stephen D. Gillies, Amy K. Erbe, Alexander L. Rakhmilevich, and Paul M. Sondel. "Short-course neoadjuvant intratumoral immunotherapy establishes immunologic memory in murine melanoma." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e21561-e21561. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e21561.

Повний текст джерела

Анотація:

e21561 Background: GD2 is disialoganglioside preferentially expressed in neuroblastoma and melanoma and anti-GD2 directed therapies are used clinically in neuroblastoma, with ongoing clinical trials in melanoma. We are currently developing an in situ vaccination approach using intratumoral (IT) delivery of an immunocytokine (IC) consisting of IL-2 linked to an anti-GD2 monoclonal antibody. While IT-IC monotherapy does not cure mice bearing established B78 melanoma tumors, it is effective when combined with local radiation therapy (RT). Here, we tested whether short course IT-IC monotherapy prior to surgical resection could result in a robust adaptive immune response preventing tumor recurrence following rechallenge after surgery. Methods: Mice bearing 50-100mm3 GD2-expressing melanoma (B78) tumors were treated with a 5-day course of 50μg IT-IC and complete surgical resection was performed 3 days following the final treatment. The immune infiltrate of resected tumors was assessed by flow cytometry. Rechallenge experiments consisted of either 2x106 B78 cells injected into the contralateral flank or 2x105 B16-GD2 cells injected via tail vein for pulmonary metastasis rechallenge. Results: IT-IC treated tumors had fewer viable tumor cells, increased CD8 T-cells, and an improved CD8:Treg ratio. Rejection of B78 contralateral flank rechallenge (implanted 40 days following surgical resection of the primary tumor) was observed in 78% (7/9) of mice treated with IT-IC compared to 50% (5/10) that received surgery alone and 0% (0/5) of naïve mice. Immunologic memory was potent in neoadjuvant-treated mice early after surgery, with all mice (5/5) rejecting contralateral B78 rechallenge that occurred on the day of surgery compared to 0% (0/5) in both surgery-alone and naïve mice. Neoadjuvant IT-IC also prevented the development of B16-GD2 lung metastasis compared to naïve mice or the surgery-alone group (when the IV injected experimental metastases were given 80 days following surgery). Conclusions: While ineffective in curing large B78 melanoma flank tumors as monotherapy, mice receiving neoadjuvant IT-IC developed robust immunologic memory preventing recurrence following surgery. The memory response was present as early as the day of surgery and was sufficient to prevent pulmonary metastasis. IT-IC should be further investigated as a neoadjuvant therapy for preventing recurrence in high-risk settings.

Стилі APA, Harvard, Vancouver, ISO та ін.

Schliemann, Christoph, Niklas Börschel, Christian Schwöppe, Rüdiger Liersch, Torsten Kessler, Martin Dreyling, Wolfram Klapper, et al. "Targeting Interleukin-2 to the Neovasculature Potentiates Rituximab‘s Activity Against Mantle Cell Lymphoma in Mice." Blood 120, no. 21 (November 16, 2012): 3716. http://dx.doi.org/10.1182/blood.v120.21.3716.3716.

Повний текст джерела

Анотація:

Abstract Abstract 3716 Introduction: Antibody-based tumor targeting strategies promise to specifically target anti-neoplastic agents (e.g. radionuclides, drugs, cytokines) to the tumor site while sparing healthy tissues. In this context, the selective delivery of bioactive molecules to the vasculature seems particularly attractive, considering the fact that antigens expressed in blood vessels are the most accessible structures within a tumor mass and that a vigorous neo-vasculature development is a common feature of virtually all solid and hematologic malignancies. Vascular targeting antibodies functionalized with different payloads are currently being investigated in patients with solid tumors and are increasingly being considered also for the treatment of hematological malignancies. In the present work, we evaluated the efficacy of the fusion protein L19-IL2, comprising the human monoclonal antibody fragment scFv(L19) linked to the cytokine Interleukin-2 (IL-2), against Mantle Cell Lymphoma (MCL), a disease for which existing therapeutic approaches still remain highly unsatisfactory. Methods: Expression of the extra-domain B of fibronectin (EDB-Fn), a well-characterized marker of angiogenic blood vessels, was analyzed in Granta-519 and HBL-2 MCL xenografts and human MCL specimens using immunohistochemistry and dual-color immunofluorescence. The in vivo targeting performance of the EDB-Fn targeting immunocytokine L19-IL2 was investigated using ex vivo immunofluorescence analyses. SCID mice xenografted subcutaneously with Granta-519 or intravenously with HBL-2 MCL cells were used for mono- and combination therapy experiments, featuring i.v. injections of L19-IL2 (30 μg, corresponding to 9.9 μg or 177000 IU rIL-2 equivalents), unconjugated rIL-2 (9.9 μg), the anti-CD20 antibody rituximab (200 μg), rituximab plus IL-2, rituximab plus L19-IL2 or saline. Results: In vivo, L19-IL2 selectively homed to EDB-Fn expressing angiogenic blood vessels, thereby mediating the accumulation of IL-2 in MCL lesions. In mono-therapy experiments, L19-IL2 showed a superior anti-lymphoma activity compared to equimolar amounts of non-targeted recombinant IL-2. In combination with rituximab, L19-IL2 induced complete remissions (CR) of established subcutaneous Granta-519 tumors in 75 % (6/8) of the cases, whereas rituximab alone or in combination with free IL-2 only delayed lymphoma progression. Mice that experienced lymphoma relapse after having achieved a CR responded a second time to L19-IL2 and rituximab treatment. In the systemic HBL-2 MCL model, the combination of L19-IL2 and rituximab almost doubled survival of mice as compared to IL-2 and rituximab (median survival 63 vs. 33 days). Conclusions: In summary, we show that the vascular targeting immunocytokine L19-IL2 promotes a potent anti-lymphoma response in combination with anti-CD20 immunotherapy. The clinical evaluation of this combination is facilitated by the fact that L19-IL2 is entirely human and already being studied in Phase II clinical trials in patients with solid tumors. Disclosures: Menssen: Philogen: Employment. Neri:Philogen: Dario Neri is a co-founder and shareholder of Philogen, the biotech company which has licensed the L19 antibody from the ETH Zurich Other, Equity Ownership.

Стилі APA, Harvard, Vancouver, ISO та ін.

Niglio, Scot Anthony, Daniel da Motta Girardi, Lisa M. Cordes, Lisa Ley, Marissa Mallek, Olena Sierra Ortiz, Jacqueline Cadena, et al. "A phase I study of bintrafusp alfa (M7824) and NHS-IL12 (M9241) alone and in combination with stereotactic body radiation therapy (SBRT) in adults with metastatic non-prostate genitourinary malignancies." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): TPS4599. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.tps4599.

Повний текст джерела

Анотація:

TPS4599 Background: The majority of non- prostate genitourinary (GU) cancers are lethal when metastatic and rare GU cancers have limited treatment options. Bintrafusp alfa is a bifunctional fusion protein composed of human TGF-β receptor II, which sequesters or “traps” all three TGF-β isoforms and a monoclonal PD-L1 antibody. NHS-IL12 is an immunocytokine composed of two IL-12 heterodimers, each fused to the H-chain of the NHS76 antibody. The NHS76 IgG1 antibody has affinity for both single- and double-stranded DNA (dsDNA) allowing for targeted delivery of pro-inflammatory cytokine, IL-12, to necrotic portions of tumor with DNA exposure to promote local immunomodulation. Preclinical data suggest synergy between these two agents. There is also evidence suggesting that stereotactic body radiation therapy (SBRT) can promote anti-tumor immune responses both locally and systemically while also synergizing with immune checkpoint inhibitors. Therefore, the combination of Bintrafusp alfa, NHS-IL12 and radiation is a potential strategy for metastatic non-prostate GU tumors. Methods: This is an open label, non-randomized, three-stage phase I trial of bintrafusp alfa and NHS-IL12 or bintrafusp alfa and NHS-IL12 in combination with either sequential or concurrent SBRT. Bintrafusp alfa (IV 1200 mg q2w) and SBRT (8 Gy x 3 fractions) are planned with a deescalating NHS-IL12 (subQ q4w) dose schedule. The accrual ceiling has been set at 66 patients. The trial will enroll patients with a pathologically confirmed diagnosis of metastatic non-prostate genitourinary cancer with an ECOG ≤ 2 (KPS ≥60%). Participants may have had prior cancer immunotherapy but excluding prior treatment with bintrafusp alfa and/or NHS-IL12. 9 patients will receive treatment in cycles consisting of 4 weeks. The primary objective is to determine the safety and highest tolerated doses with acceptable toxicity (recommended phase II dose) of bintrafusp alfa and NHS-IL12 alone or in combination with SBRT administered sequentially or concurrently in patients with metastatic non-prostate genitourinary cancers. Secondary objectives are objective response rate (ORR), progression free survival (PFS) and overall survival (OS). Exploratory objectives are to determine peripheral immune modulation and the status of the immune microenvironment using cytokine analysis, circulating tumor cells, multiplex immunohistochemistry, T-cell receptor sequencing, and RNA-sequencing. The study is open and enrolling. Clinical trial information: NCT04235777.

Стилі APA, Harvard, Vancouver, ISO та ін.

Berdel, Andrew F., Christoph Rollig, Martin Wermke, Linus Angenendt, Leo Ruhnke, Jan-Henrik Mikesch, Teresa Hemmerle, et al. "A Phase I Trial of the Antibody-Cytokine Fusion Protein F16IL2 in Combination with Anti-CD33 Immunotherapy for Posttransplant AML Relapse." Blood 138, Supplement 1 (November 5, 2021): 2345. http://dx.doi.org/10.1182/blood-2021-145859.

Повний текст джерела

Анотація:

Abstract Introduction Natural killer (NK) cells are key effectors in cancer immunosurveillance and posttransplant immunity, but shortage of environmental growth factors and deficient recognition of malignant cells may limit their anticancer efficacy. We hypothesized that the antibody-mediated anchoring of interleukin-2 (IL-2) to the leukemia-modified extracellular matrix (ECM) would increase NK cell abundance and activity to potentiate antibody-dependent cellular cytotoxicity (ADCC) against acute myeloid leukemia (AML) blasts. In this novel-novel combination dose-escalation phase 1 trial, we enrolled patients with AML relapse after allogeneic hematopoietic stem cell transplantation (HSCT) to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary activity of F16IL2, an antibody-cytokine fusion protein composed of the human antibody fragment scFv(F16) in diabody format and two molecules of human IL-2, in combination with the Fc-optimized, ADCC-mediating anti-CD33 monoclonal antibody BI 836858. F16 specifically targets the A1 domain of the ECM protein tenascin C (TnC), which is spliced into the TnC molecule during active angiogenesis and tissue remodeling while it is virtually absent in normal tissues. Methods F16IL2 (10 - 20 Mio IU IV) was administered on days 1, 8, 15 and 22 of 28-day cycles, followed by administration of BI 836858 (10 - 40 mg IV) two days after each F16IL2 infusion. Dose escalation was performed over 4 dose levels (DL). Cohort 1 (10 Mio IU F16IL2 and 10 mg BI 836858, n = 5), cohort 2 (10 Mio IU F16IL2 and 20 mg BI 836858, n = 3), cohort 3 (20 Mio IU F16IL2 and 20 mg BI 836858, n = 4), cohort 4 (20 Mio IU F16IL2 and 40 mg BI 836858, n = 3). Safety and tolerability, pharmacodynamics and -kinetics, clinical efficacy and immune effector cell dynamics were investigated. This trial was registered at EudraCT as #2015-004763-37. Results Between December 2016 and March 2020, 15 patients with a median age of 50 years (range, 20 - 68) were enrolled and treated across 4 dose levels. Six patients (40%) had received two or more prior HSCT. The most frequent drug-related AEs (F16IL2 or BI 836858 or combination) were pyrexia (n = 13, 87%), chills (n = 12, 80%) and infusion-related reactions (n = 9, 60%), consistent with the expected toxicity profile of cytokine-armed or naked mAbs. These events were generally manageable, transient and of grade ≤ 2. One dose-limiting toxicity occurred at each of DL 3 (pulmonary edema) and 4 (acute GVHD). No patient died within the first 30 days of treatment initiation. Whereas no formal maximum tolerated dose (MTD) was reached, the maximum tested dose of 20 Mio IU F16IL2 and 40 mg BI 836858 was considered the recommended dose (RD). Three objective responses (1 CR, 1 CRi, 1 PR in extramedullary AML) were observed among 7 patients treated at the two higher DL, whereas no responses occurred at the two starting DL. Median OS among all 15 patients was 4.8 months (1.5 - 12.9), with a 6- and 12-month OS of 40% and 27%, respectively. Among those 7 patients whose AML was at least temporarily controlled with study treatment (CR/CRi, PR, SD), 12-month OS was 67% vs. 0% in non-responders. Combination therapy stimulated the expansion and activation of NK cells in bone marrow and peripheral blood. Conclusions To the best of our knowledge, this is the first study demonstrating that the strategy of potentiating ADCC with tumor-targeted immunocytokines is feasible in humans. In the difficult-to-treat situation of posttransplant AML relapse, responses were observed at higher DL, even in patients with extramedullary disease. The antibody-mediated targeted delivery of IL-2 to the ECM combined with anti-CD33 immunotherapy represents an innovative experimental approach associated with acceptable safety and encouraging biologic and clinical activity in posttransplant AML relapse. Disclosures Wermke: Novartis, Roche, Pfizer, BMS: Consultancy, Honoraria, Research Funding. Hemmerle: Philogen S.p.A.: Current Employment. Schäfers: Philogen S.p.A.: Research Funding. Rossig: BMS and Celgene: Honoraria; Pfizer: Honoraria; Novartis: Honoraria; AdBoards by Amgen: Honoraria. Stelljes: Pfizer: Consultancy, Research Funding, Speakers Bureau; Kite/Gilead: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Celgene/BMS: Consultancy, Speakers Bureau; Medac: Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Rueter: Boehringer Ingelheim Pharma GmbH & Co. KG: Current Employment. Neri: Philogen S.p.A.: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Multiple patents on vascular targeting; ETH Zurich: Patents & Royalties: CD117xCD3 TEA. Berdel: Philogen S.p.A.: Consultancy, Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees. Schliemann: Roche: Consultancy; Philogen S.p.A.: Consultancy, Honoraria, Research Funding; Astellas: Consultancy; Pfizer: Consultancy; BMS: Consultancy, Other: travel grants; Boehringer-Ingelheim: Research Funding; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding; AstraZeneca: Consultancy; Abbvie: Consultancy, Other: travel grants.

Стилі APA, Harvard, Vancouver, ISO та ін.

Pelegrin, Mireia, Laurent Gros, Hanna Dreja, and Marc Piechaczyk. "Monoclonal Antibody-based Genetic Immunotherapy." Current Gene Therapy 4, no. 3 (September 1, 2004): 347–56. http://dx.doi.org/10.2174/1566523043346246.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Schuster, James M., and Darell D. Bigner. "Immunotherapy and monoclonal antibody therapies." Current Opinion in Oncology 4, no. 3 (June 1992): 547–52. http://dx.doi.org/10.1097/00001622-199206000-00020.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Mehra, NarinderK. "Antibody therapy: Substitution-immunomodulation -monoclonal immunotherapy." Indian Journal of Medical Research 149, no. 4 (2019): 563. http://dx.doi.org/10.4103/ijmr.ijmr_2198_18.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Більше джерел

Дисертації з теми "Monoclonal antibody, immunocytokine, immunotherapy"

Nadal, Lisa. "Isolation and validation of novel monoclonal antibodies targeting the tumor microenvironment for the selective delivery of cytokines payloads." Doctoral thesis, Università degli studi di Trento, 2021. http://hdl.handle.net/11572/323258.

Повний текст джерела

Анотація:

Cancer immunotherapy has revolutionized the field of oncology by giving the possibility to ligands (e.g., antibodies) to selectively target tumor antigens and accumulate at the site of the disease while sparing normal tissues. During the past years, the number of patient eligible for immune-based cancer treatments has seen an exponential increase as these therapies are becoming first line treatment for many cancer indications. A promising anticancer strategy consists in the targeted delivery of bioactive compounds (e.g., cytokines) to the tumor microenvironment with high-affinity ligands specific for tumor-associated antigens. This approach improves the efficacy of the drug by reducing related side effects and increasing the therapeutic index of the payload. Currently, antibodies represent one of the most successful class of ligands used for this purpose as they can be generated against virtually any antigen. Many methodologies have been described for the generation and isolation of antibodies with high antigen-binding specificity. Among these, phage display technology has emerged as a powerful and versatile tool for the in vitro discovery of antibodies and peptides. Since it was invented in mid 1980s, phage-display has paved the way to the generation of more than 70 phage–derived monoclonal antibodies (mAbs) that entered clinical studies, and 14 of which have been approved in the market. Cytokines are proteins capable of modulating the activity of the immune system and some cytokine-products have gained marketing authorization for the treatment of cancer. In order to increase the therapeutic index of cytokine payloads, the generation of fusion proteins with tumor-homing antibodies has been proposed. These so-called “immunocytokine” products constitute a class of “armed” antibody products, in which a tumor-targeting immunoglobulin is fused with a cytokine. In this thesis, we present the generation and characterization of antibodies specific for two tumor microenvironment-associated antigens: Tenascin C and Fibroblast Activation Protein. Both antigens are undetectable in healthy tissues but abundantly expressed in the tumor stroma. In the first part of the thesis, we have isolated antibodies specific for the spliced domain D of Tenascin C from the synthetic phage library “ETH2Gold”. Antibodies were affinity matured randomizing key residues of CDR1 of heavy and light chains. The highest affinity clone, R6N, was characterized in vitro and in vivo showing selective accumulation at the tumor site in mouse models of cancer. An immunocytokine featuring IL12 as payload has been generated and its therapeutic activity evaluated in tumor bearing mice. R6N-IL12 exhibited potent antitumor activity in immunodeficient mice bearing SKRC52 renal cell carcinoma, as well as in immunocompetent mice bearing SMA-497 glioma. In the second part of this thesis, a monoclonal antibody has been isolated against Fibroblast Activation Protein. After affinity maturation of the CDR2 of heavy and light chains of the parental antibody C5, the selected 7NP2 antibody showed improved affinity and excellent tumor targeting properties in SKRC52-hFAP tumor bearing mice. When fused to IL12, 7NP2 was able to induce tumor growth retardation and tumor remission in mouse models of cancer. Collectively, in this thesis we have isolated and validated two monoclonal antibodies selective for tumor microenvironment-associated antigens. Both antibodies when fused to IL12 induced tumor growth retardation and remission in immunodeficient and immunocompetent mouse models providing a rationale for possible future applications of R6N and 7NP2 antibodies for the treatment of cancer patients.

Стилі APA, Harvard, Vancouver, ISO та ін.

Nicholson, Stephen. "Immune responses following monoclonal antibody therapy of ovarian cancer." Thesis, Imperial College London, 2000. http://hdl.handle.net/10044/1/8395.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Mehta, Payal. "Molecular Analysis of Regulation of Macrophage Fcγ Receptor Function: Implications for Tumor Immunotherapy". The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1313606589.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Gustafsson, Liljefors Maria. "Immunotherapy with the anti-EpCAM monoclonal antibody and cytokines in patients with colorectal cancer : a clinical and experimental study /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-499-6/.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Turrini, Riccardo. "Targeting BARF1 for the therapeutic control of EBV-associated malignancies." Doctoral thesis, Università degli studi di Padova, 2010. http://hdl.handle.net/11577/3427092.

Повний текст джерела

Анотація:

The Epstein-Barr virus is a y-herpesvirus that preferentially infects human Blymphocytes. It is estimated that 95% of worldwide population is infected, but usually the infection happens during childhood and is asymptomatic. Beside the association to a self-limiting lymphoproliferative disease, infectious mononucleosis, the virus is related to the development of some human cancerous forms, which are characterized by different patterns of viral latency, like Burkitt’s lymphoma (BL) and some forms of gastric carcinoma (GC), Hodgkin’s lymphoma (HL) and nasopharyngeal carcinoma (NPC), and, finally, PTLD, post-transplant lymphoproliferative diseases. In addition to the latency genes, it is known the expression of different non-polyadenilated RNA (EBER) and, especially in the cases of NPC and GC, the expression of a transmembrane protein belonging to the lytic cycle, BARF1. BARF1 is a 221-aa protein with a transmembrane domain at the C-terminal. Only recently, its transforming and immortalizing roles have been demonstrated in human cells. Moreover, its extracellular domain can be cleaved and can act in a paracrin way as a growth factor on bystander cells, and it owns mitogenic activities. Nevertheless, its mitogenic and mutagenic properties are not well understood yet, but the importance of this protein in the pathways of neoplastic progression and its expression only on infected cells (or at the surface of those that can bind its secreted forms) render BARF1 an optimal target for a therapeutic approach of EBV-related tumours. Different strategies for the treatment of EBV-related neoplasms are currently in use in clinic. Some strategies reside on the reduction of the immunosuppressive regimen, on the exploitation of gene therapy, on the use of chemotherapy or antiviral drugs, or on the approaches of immunotherapy. The use of autologous or HLA-matched cytotoxic T lymphocytes (CTL) proved to be efficient and usually devoided of side effects, especially for PTLD patients. A different aspect of immunotherapy is based on the use of monoclonal antibodies (mAb), as it was already demonstrated in different clinical settings by the use of rituximab. In this PhD work, the generation and the in vitro evaluation of different monoclonal antibodies specific for BARF1 are described. Moreover, once their activity was established on cell culture in vitro, this approach was translated to some pre-clinical models, using immunodeficient mice bearing EBV-positive tumours. Also in these experiments, the antibodies proved to be therapeutically efficient. On one side, the use of mAb for the diagnosis and for the cure of malignancies is acquiring an increasing importance in the clinic, thanks to the specificity of action of these molecules and to their relative easiness of use, if compared to the cellular adoptive therapy. On the other side, although BARF1 functions and interactions with other proteins or cells are not well studied yet, it can be regarded as a promising target for EBV-related malignancies, since it is expressed in NPC and GC and owns important transforming properties, while being a lytic cycle protein.
Il virus di Epstein-Barr è un γ-herpesvirus che infetta preferenzialmente i linfociti B umani. Si stima che il 95% della popolazione mondiale sia infettata, ma normalmente tale infezione avviene nell’infanzia ed è asintomatica. Oltre ad essere l'agente causale di una malattia linfoproliferativa autolimitante, la mononucleosi infettiva, la presenza del virus è associata ad alcune neoplasie umane, caratterizzate da diversi pattern di espressione genetica. Alcune delle neoplasie EBV-associate sono il linfoma di Burkitt (BL) e alcune forme di carcinoma gastrico (GC), il linfoma di Hodgkin (HL) e il carcinoma nasofaringeo (NPC), e infine le malattie linfoproliferative post-trapianto (PTLD). Oltre ai geni di latenza, è nota l’espressione di diversi RNA non poliadenilati (EBER) e, soprattutto nei casi di NPC e di GC, l’espressione da parte delle cellule infettate di una proteina transmembrana del ciclo litico, BARF1. BARF1 è una proteina di 221 aminoacidi, con una porzione transmembrana al C-terminale. Solo recentemente ne è stato dimostrato il ruolo trasformante ed immortalizzante in cellule umane. Inoltre, il dominio extracellulare può essere tagliato, ed è in grado di agire in modo paracrino come fattore di crescita per le cellule adiacenti, possedendo infatti attività mitogena. In generale, tuttavia, le attività mitogene e mutagene non sono state ancora completamente elucidate, ma l’importanza di questa proteina nei pathway di progressione neoplastica e la sua espressione unicamente nelle cellule infettate (o in quelle che ne legano la forma secreta) la rendono un ottimo candidato come bersaglio per un approccio terapeutico delle neoplasie EBV-correlate. Esistono diversi orientamenti terapeutici nei confronti delle neoplasie EBV-relate; alcune strategie prevedono la riduzione del regime di immunosoppressione, soprattutto per il trattamento di PTLD, la somministrazione di farmaci antivirali, la terapia genica, l’uso di chemioterapici e approcci di immunoterapia. L’uso di linfociti T citotossici (CTL) autologhi o da donatori compatibili si è dimostrata efficace e generalmente priva di effetti collaterali, soprattutto in pazienti affetti da PTLD. Un altro aspetto dell’immunoterapia prevede l’utilizzo di anticorpi monoclonali (mAb), come già dimostrato in ambito clinico dall'utilizzo di rituximab. In questo progetto di Dottorato viene descritta la generazione e la valutazione in vitro di diversi anticorpi monoclonali specifici per BARF1. Inoltre, una volta dimostratane l'attività su colture cellulari in vitro, si è traslato l'approccio ad alcuni modelli pre-clinici sfruttando topi immunodeficienti portatori di tumore EBV-positivo. Anche in questi esperimenti è stato possibile dimostrare l'efficacia terapeutica degli anticorpi prodotti. Da un lato, l’utilizzo di mAb sia nella diagnosi che nella cura di neoplasie sta assumendo un’importanza crescente in ambito clinico, grazie alla specificità di azione di queste molecole e alla loro relativa facilità d’uso, soprattutto se paragonati all’immunoterapia cellulare adottiva. Dall’altro, BARF1, benchè non ne siano ancora state completamente studiate le funzioni e le interconnessioni con altre molecole o cellule, è sicuramente un target promettente per i tumori EBV-relati, in quanto, nonostante sia una proteina espressa durante il ciclo litico, è presente soprattutto nei casi di NPC e di GC, e possiede importanti funzioni trasformanti, anche con azione paracrina.

Стилі APA, Harvard, Vancouver, ISO та ін.

RIZZUTO, MARIA ANTONIETTA. "Exploiting Nanotechnology to Improve Cancer Immunotherapy and Overcome Biological Barriers." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2019. http://hdl.handle.net/10281/241065.

Повний текст джерела

Анотація:

L’utilizzo in clinica di anticorpi monoclonali (mAbs) ha rivoluzionato il trattamento del cancro. Negli ultimi 20 anni gli mAbs sono stati molto usati anche nel campo delle nanotecnologie dove, l’elevata specificità e selettività verso i target è stata sfruttata per aumentare la specificità di legame delle nanoparticelle (NPs) verso il bersaglio farmacologico, riducendo gli effetti collaterali dovuti alla diffusione passiva. Ad ogni modo, ad oggi, le implicazioni terapeutiche e gli effetti della coniugazione degli anticorpi sulle NPs, sono ancora poco considerati. In questa tesi mi sono focalizzata sullo studio di tumori per i quali non esistono ancora terapie adeguate, quali i tumori al cervello e al seno triplo negativo (TNBC), allo scopo di sfruttare le NPs come strumento per incrementare l’efficacia delle terapie basate sull’uso di mAbs. In particolare, il mio lavoro ha avuto come scopo l’incremento dello spettro di azione di mAbs, già approvati per uso clinico, rendendoli adatti a nuove applicazioni terapeutiche, sia come proteina intera sia come frammenti. Nel primo capitolo ho utilizzato una variante ricombinante di ferritina umana (HFn) come nanovettore per promuovere l’attraversamento della barriera emato-encefalica (BEE) di mAbs al fine di attivare la risposta immunitaria ADCC contro le cellule tumorali di cancro al cervello. Come modelli tumorali sono stati selezionati un tumore primario (Glioblastoma Multiforme) e un tumore secondario con metastasi cerebrali (tumore al seno HER2 positivo). HFn è stata scelta come sistema di trasporto grazie alla sua capacità di attraversare la BEE a seguito dell’interazione con il recettore TfR1. Ad essa ho coniugato gli anticorpi Trastuzumab e Cetuximab ed ho confermato, tramite saggi in vitro, il mantenimento della specificità di legame verso i target per entrambe le specie proteiche. Inoltre, ho valutato che, in seguito alla coniugazione su HFn, entrambi gli mAbs mantenessero le loro attività tossiche sulle cellule bersaglio. Infine, ho confermato che il nanoconiugato fosse in grado di attraversare un modello in vitro di BEE e che, dopo il passaggio, l’anticorpo mantenesse intatta la sua attività citotossica. Pertanto, i risultati preliminari ottenuti propongono HFn come promettente sistema per il trasporto di mAbs oltre la BEE per il trattamento di patologie cerebrali. Nel secondo capitolo, invece, ho coniugato le singole catene dell’anticorpo Cetuximab (CTX) a nanoparticelle di ossido di ferro, al fine di indagarne l’utilizzo come possibili surrogati dell’anticorpo intero nel trattamento del TNBC. Per questo studio abbiamo selezionato 3 linee cellulari di TNBC che differissero sia in termini di mutazioni di proteine coinvolte nella via di trasduzione del segnale del recettore EGFR, sia in termini di responsività al trattamento con CTX. In questo studio abbiamo indagato la specificità di legame verso il recettore, la capacità di interferire con i pathways molecolari, l’effetto sulla proliferazione e sul ciclo cellulare, l’apoptosi indotta e l’attivazione della risposta immunitaria ADCC, confrontando sempre l’azione del nanoconiugato con quella di CTX. I dati ottenuti hanno dimostrato che la nanoformulazione è in grado di migliorare l’azione tossica dell’anticorpo nelle cellule sensibili al trattamento con CTX ma, inaspettatamente, anche in cellule TNBC resistenti. Inoltre, i saggi di proliferazione e di analisi delle vie di segnalazione a valle, hanno evidenziato che la nanoformulazione è in grado di esercitare la sua azione attivando meccanismi molecolari differenti rispetto al CTX, permettendo l’elusione dei meccanismi di resistenza. I dati ottenuti mettono in evidenza l’enorme potenziale terapeutico della nostra nanoformulazione nel trattamento del TNBC. Nel dettaglio, la nanoformulazione potrebbe migliorare l’efficacia del trattamento con Cetuximab, riducendo anche le dosi, in tumori sensibili e resistenti.
The use of therapeutic monoclonal antibodies (mAbs) has revolutionized cancer treatment. During the last decades, mAbs became very appealing also for nanotechnology. Indeed, they have been exploited as targeting moieties for nanoparticles, thanks to their high binding efficacy and target selectivity. However, the functionalization of NPs with mAbs is usually performed with the aim to ameliorate targeting, rather than to overcome mAbs limitations. Moreover, the therapeutic implications of nanoconjugation are generally poorly considered. In this thesis, I focused on the study of cancers with no efficient therapies available, such as brain cancers and triple negative breast cancer (TNBC), with the final goal to exploit nanoparticle (NP) conjugation as a tool to improve antibody-based therapies. In particular my work aimed at increasing the spectrum of action of already existing mAbs, making them suitable for new applications, either as the whole protein or as fragments. In Chapter 1, I used a recombinant human ferritin (HFn) as nanovector to promote mAbs permeation across the BBB to activate the ADCC response against brain cancer. Glioblastoma and HER2+ metastatic breast cancer were selected as brain tumor models. HFn was used as delivery system thanks to the ability to cross the BBB upon interaction with its receptor. Then, cetuximab or trastuzumab were linked to HFn and the maintenance of the cytotoxic activity of NPs was confirmed by in vitro assays. Next, we tested the ability of HFn- mAb to cross an in vitro model of BBB. Results showed that HFn-mAb proved to be effective in BBB crossing and that, after permeation, mAbs retained their biological activity against the targets, as assessed by MTS and ADCC assays. i These preliminary results support the use of HFn as efficient carrier to enhance mAbs permeation into the brain, without affecting their activity. In Chapter 2, half-chain fragments of cetuximab were conjugated to colloidal NPs (HC-CTX-NPs) to be investigated as surrogates of mAbs in TNBC. Three TNBC cell lines were selected according to EGFR expression and to diverse cetuximab sensitivity. The molecular mechanisms of action of HC-CTX- NPs, including cell targeting, interference with signaling pathways, proliferation, cell cycle, apoptosis and ADCC response, were investigated in TNBC cells. We found that HC-CTX-NPs were able to enhance the therapeutic efficacy and improve the target selectivity against sensitive, but unexpectedly also resistant, TNBC cells. Viability assays and signaling transduction modulation suggested that HC-CTX-NPs not only improved the antibody activity but also exerted different mechanisms of action to circumvent CTX resistance. Our results provide robust evidence of the potential of HC-CTX-NPs in the treatment of TNBC, which could improve curative efficiency, reducing dosages in both sensitive and resistant tumors.

Стилі APA, Harvard, Vancouver, ISO та ін.

Laporte, Jérôme. "Nouveaux anticorps monoclonaux contre les Yersinia pour le diagnostic et l’immunothérapie." Thesis, Paris 11, 2014. http://www.theses.fr/2014PA114834/document.

Повний текст джерела

Анотація:

Trois bactéries du genre Yersinia sont pathogènes pour l’homme : Yersinia pestis (bacille de la peste), et les bactéries entéropathogènes Yersinia pseudotuberculosis et Yersinia enterocolitica. Yersinia pestis est responsable de plus de 20 000 cas humains de peste déclarés à l’Organisation Mondiale de la Santé (OMS) ces dix dernières années dans différents foyers en Afrique, Asie et Amériques. Considérée aujourd’hui à tort comme une maladie du passé, elle est au contraire classée parmi les maladies réémergentes Même si elle ne se présente plus sous la forme d’épidémies massives, elle pose encore au monde actuel d’importants défis de par son extrême gravité, sa rapidité de dissémination, une apparition de résistances aux antibiotiques et une éventuelle utilisation terroriste du bacille. Dans ce contexte, l’immunothérapie contre Y. pestis pourrait être une bonne alternative pour traiter la peste bubonique et pulmonaire. Un des objectifs de cette thèse était de produire des anticorps monoclonaux murins contre trois protéines de l’injectisome (YscF, YscC et LcrV), un facteur de virulence clé des Yersinia. Les anticorps obtenus ont été caractérisés et pour certains leurs épitopes identifiés. Par la suite, en collaboration avec Elisabeth Carniel à l’Institut Pasteur, leur pouvoir neutralisant a été évalué in vivo dans un modèle murin de peste bubonique. Ces mêmes anticorps monoclonaux, produits contre les protéines de l’injectisome sont en cours d’évaluation pour la mise au point d’un test de diagnostic rapide de Y. pestis dans différents fluides et échantillons biologiques. Yersinia pseudotuberculosis et Yersinia enterocolitica sont présentes dans le monde entier et sont transmises par contamination à partir de viande de porc mal cuite, de lait ou produits laitiers et de végétaux, ou par contact avec des animaux porteurs sauvages ou domestiques. Une transmission interhumaine par voie fécale-orale est également possible. Ces bactéries sont responsables très fréquemment d’infections entériques. Cependant leur recherche dans les coprocultures n’est pas réalisée de façon systématique en laboratoires d’analyses médicales du fait de leur croissance lente et difficile sur les milieux usuels, ce qui rend leur isolement à partir de fèces difficile. De plus, les procédures de routine sont coûteuses et longues. Cela entraine probablement une sous-estimation de l’incidence des infections à Yersinia entéropathogènes, la prescription de traitements non adaptés et la réalisation d’appendicectomies non nécessaires, d’où la nécessité de développer des tests de diagnostic rapides, spécifiques, sensibles et faciles à utiliser. Un des objectifs de cette thèse était de produire un panel d‘anticorps monoclonaux murins contre les principaux biotypes et sérotypes pathogènes de Y. pseudotuberculosis et Y. enterocolitica pour le développement de tests de diagnostic immunologiques (ELISA et tests bandelettes) répondant aux caractéristiques recherchées et utilisables directement avec des échantillons biologiques humains
Three bacteria of the genus Yersinia are pathogenic for the human: Yersinia pestis (the plague bacillus) and the enteropathogenic bacteria: Yersinia pseudotuberculosis and Yersinia enterocolitica. Yersinia pestis is responsible for more than 20,000 human cases of plague declared to the World Health Organization (WHO) during the ten last years in different areas from Africa, Asia and America. Mistakenly considered today as a disease from the past, on the contrary, the plague is re-emerging. Even if it doesn’t occur as a massive epidemic, it still lays down a challenge to the world for its important severity, its quick spreading, the appearance of antimicrobial resistance and a potential use for terrorism. Under the circumstances, the immunotherapy against Y. pestis could be a good option to treat bubonic and pneumonic plague. One the aims of this thesis was to produce murine monoclonal antibodies against the three proteins of the injectisom (YscF, YscC, LcrV), a key virulence factor of Yersinia. The obtained antibodies were characterized and for certain, the epitopes were identified. Then, in collaboration with Elisabeth Carniel from Institut Pasteur, their therapeutic effect was evaluated in vivo with a bubonic plague model in mice. The antibodies generated against the proteins from the injectisom are now evaluated in a diagnosis test for a fast detection of Y. pestis in different biological samples. Yersinia enterocolitica and Yersinia pseudotuberculosis, the two enteropathogenic Yersinia species for humans, have a worldwide distribution and are among the most frequent agents of human diarrhea in temperate and cold countries. However, research of enteropathogenic Yersinia is not consistently performed in medical laboratories because of their specific growth characteristics, which makes their isolation from the stool samples difficult. Moreover, current procedures for isolation are expensive and time consuming, which leads to underestimation of the incidence of yersiniosis and prescriptions of inappropriate antibiotic treatments. One the aims of this thesis was to produce different murine monoclonal antibodies against the main pathogenic biotypes and serotypes of Y. pseudotuberculosis and Y. enterocolitica for the development of fast, sensitive, specific and easy-to-use immunoassays (ELISA and dipsticks), useful for both human and veterinary diagnosis

Стилі APA, Harvard, Vancouver, ISO та ін.

Sandin, Linda. "Immunomodulatory Therapy of Solid Tumors : With a Focus on Monoclonal Antibodies." Doctoral thesis, Uppsala universitet, Klinisk immunologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-210080.

Повний текст джерела

Анотація:

Cancer, historically considered a genetic disease, is currently acknowledged to affect the whole body. Our immune system is one key player that can elicit a response against malignant cells but can also promote tumorigenesis. Tumors avoid immune recognition by creating a suppressive microenvironment and inducing tolerance. T-cells are regarded a major effector cell type in tumor immunotherapy. An important ”switch” needed for T-cell activation involves so-called costimulatory and coinhibitory receptors. In this thesis, experimental tumor models were used to investigate the potential of immunomodulatory antibodies to stimulate immune cells and subsequently eliminate tumors. First, systemic antibody blockade of two negative checkpoint regulators (CTLA-4 and PD-1) present on T-cells was evaluated in combination with local CpG therapy or standard BCG treatment. Indeed, this combinatorial therapy with CpG augmented anti-tumor effects with increased levels of tumor-directed T-cells and reduced tumor-infiltrating Tregs. Secondly, as these immunomodulatory antibodies elicit severe side effects in patients, a local low-dose delivery regimen was explored as an alternative to systemic bolus treatment. Our results demonstrated that an approximately seven times lower dose of aCTLA-4, compared to systemic delivery, could eradicate both primary and distant tumors. CD40-expressing APCs are another potential target in antibody-mediated cancer therapy. CD40-stimulated dendritic cells (DCs) have the capability to activate tumor-directed T-cells to kill tumor cells. We next sought to investigate agonistic CD40 antibody efficacy and in vivo biodistribution when delivered locally compared to the equivalent systemic dose. Anti-tumor effects were dependent on CD8+ T-cells, host CD40 expression and the presence of tumor antigen at the injection site. CD40 antibodies were cleared from the circulation and accumulated in lymphoid organs, where, upon repeated aCD40 dosing, target APC populations increased in numbers and upregulated their surface CD40 expression. Lastly, CD40 agonist antibodies were mixed with nanoparticles to enhance their stimulatory properties. B-cells demonstrated increased proliferative capacity and DCs became more activated when exposed to the cocktail. Further, this combination reduced serum levels of pro-inflammatory cytokines compared to plain antibodies. The results herein advocate further exploratory studies of the delivery of monoclonal antibodies at the tumor site in order to improve anti-tumor effects and reduce toxicity.

Стилі APA, Harvard, Vancouver, ISO та ін.

Heitzmann-Daverton, Adèle. "Utilisation d'un anticorps monoclonal anti-Tn en immunothérapie des cancers." Phd thesis, Université René Descartes - Paris V, 2013. http://tel.archives-ouvertes.fr/tel-00923181.

Повний текст джерела

Анотація:

La transformation des cellules normales de l'organisme en un phénotype malin est souvent accompagnée de changements dans leur antigénicité. L'antigène Tn (GalNac-O-Ser/Thréo) est un antigène (Ag) glycopeptidique spécifique des tumeurs et exprimé à la membrane plasmique des cellules cancéreuses dans la majorité des carcinomes humains ainsi que dans certaines tumeurs hématologiques, tandis qu'il n'est pas détecté dans les cellules normales. Il représente donc une cible potentielle très intéressante pour l'immunothérapie passive par anticorps, car il n'est pas détectable dans les cellules normales, mais est démasqué dans environ 90% des cancers épithéliaux du fait d'une dérégulation des processus de glycosylation. Les anticorps monoclonaux (AcM) spécifiques d'antigènes exprimés à la membrane des cellules tumorales ont une efficacité prouvée dans le traitement de certains cancers. Ces AcM thérapeutiques sont particulièrement intéressants pour le traitement des cancers du fait de leur forte spécificité pour les cellules tumorales et de leur faible toxicité pour les cellules normales, contrairement aux chimiothérapies conventionnelles, mais leur mécanisme d'action est encore mal connu. L'AcM Chi-Tn est un anticorps chimérique homme/souris capable de se fixer de façon spécifique à l'antigène tumoral Tn, alors qu'il ne se fixe pas sur les cellules normales. Cet AcM pourrait donc être envisagé comme agent thérapeutique dans le traitement des cancers épithéliaux par immunothérapie passive.Nous nous sommes intéressés à l'AcM Chi-Tn non couplé en vue d'analyser son mécanisme d'action et d'évaluer son efficacité thérapeutique in vivo. Nous avons montré que l'AcM Chi-Tn seul ne possède pas d'effet toxique direct sur les lignées de cellules tumorales Tn-positives in vitro. Cependant, en présence de macrophages, cet AcM est capable d'induire la lyse de ces cellules par un mécanisme d'ADCC. In vivo, l'AcM Chi-Tn, associé à la cyclophosphamide, induit le rejet d'une tumeur du sein dans plus de 80% des souris. Cette inhibition de la croissance tumorale est abolie chez les souris déficientes pour la chaine associée aux récepteurs RFc activateurs, suggérant in vivo un mécanisme d'ADCC. Par l'étude microscopique du microenvironnement tumoral, nous avons observé que les cellules tumorales forment in vivo des synapses avec des macrophages, des neutrophiles, mais aussi des lymphocytes B. Des expériences de survie in vivo chez des souris déficientes pour différentes populations cellulaires montrent que les lymphocytes T semblent nécessaires à la protection des souris par Chi-Tn contre la tumeur. Ainsi, ces résultats confirment le rôle des effecteurs exprimant des RFc activateurs, mais aussi le rôle indispensable de la réponse immune adaptative pour assurer l'effet thérapeutique des AcM.Nous nous sommes également intéressés à l'utilisation potentielle de l'AcM Chi-Tn comme vecteur d'agents cytotoxiques. In vivo, dans un modèle de tumeurs solides chez la souris, des expériences de biodistribution montrent que l'AcM Chi-Tn est capable de cibler spécifiquement les zones tumorales, ce qui en fait un anticorps potentiellement utilisable comme vecteur de molécules toxiques. L'internalisation du complexe anticorps/antigène cible est un pré-requis nécessaire à l'utilisation de l'anticorps conjugué. Nous avons montré in vitro que l'AcM Chi-Tn est internalisé dans les endosomes précoces et de recyclage pendant un temps relativement long, faisant de cet AcM un bon candidat pour être couplé à des agents cytotoxiques. Durant ma thèse, nous avons couplé l'AcM Chi-Tn à la toxine saporine ou à la molécule cytotoxique auristatine F, et nous avons montré in vitro que ces conjugués sont cytotoxiques sur des lignées cellulaires Tn-positives.

Стилі APA, Harvard, Vancouver, ISO та ін.

Fagerqvist, Therese. "Studies of α-synuclein Oligomers-with Relevance to Lewy Body Disorders". Doctoral thesis, Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-204466.

Повний текст джерела

Анотація:

The protein alpha-synuclein (α-synuclein) accumulates in the brain in disorders such as Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). It is believed that the monomeric form of α-synuclein can adopt a partially folded structure and start to aggregate and form intermediately sized oligomers or protofibrils. The aggregation process can continue with the formation of insoluble fibrils, which are deposited as Lewy bodies. The oligomers/protofibrils have been shown to be toxic to neurons and are therefore believed to be involved in the pathogenesis of the actual diseases. The overall aims of this thesis were to investigate the properties of α-synuclein oligomers and to generate and characterize antibodies against these species. In addition, the potential for immunotherapy of the α-synuclein oligomer-selective antibodies were evaluated in a transgenic mouse model with α-synuclein pathology. Stable, β-sheet rich α-synuclein oligomers were induced by incubation with either one of the reactive aldehydes 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE). The oligomers exhibited distinct morphological properties, although both types were toxic when added to a neuroblastoma cell line. The seeding effects of ONE-induced oligomers were studied in vitro and in vivo. The oligomers induced seeding of monomeric α-synuclein in a fibrillization assay but not in a cell model or when injected intracerebrally in transgenic mice. It seemed, however, as if the oligomers affected α-synuclein turnover in the cell model. By immunizing mice with HNE-induced oligomers antibody producing hybridomas were generated. Three monoclonal antibodies were found to have strong selectivity for α-synuclein oligomers. These antibodies recognized Lewy body pathology in brains from patients with PD and DLB as well as inclusions in the brain from young α-synuclein transgenic mice, but did not bind to other amyloidogenic proteins. Finally, immunotherapy with one of the oligomer/protofibril selective antibodies resulted in lower levels of such α-synuclein species in the spinal cord of α-synuclein transgenic mice. To conclude, this thesis has focused on characterizing properties of α-synuclein oligomers. In particular, antibodies selectively targeting such neurotoxic forms were generated and evaluated for passive immunization in a transgenic mouse model. Such immunotherapy may represent a future treatment strategy against Lewy body disorders.

Стилі APA, Harvard, Vancouver, ISO та ін.

Книги з теми "Monoclonal antibody, immunocytokine, immunotherapy"

1960-, Grossbard Michael L., ed. Monoclonal antibody-based therapy of cancer. New York: Dekker, 1998.

Знайти повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

A, Foon Kenneth, and Morgan Alton C, eds. Monoclonal antibody therapy of human cancer. Boston: Nijhoff, 1985.

Знайти повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Rodriguez, Andrės Felipe. Successful immunotherapy to malignant cells with monoclonal antibody to suppressor T cells. [New Haven: s.n.], 1988.

Знайти повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Frost & Sullivan., ed. U.S. monoclonal antibody markets: Manufacturers struggling for regulatory approval. Mountain View, Calif: Frost & Sullivan, 1994.

Знайти повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

1927-, Baldwin R. W., Byers Vera S, and Mann Ronald D. 1928-, eds. Monoclonal antibodies and immunoconjugates. Carnforth, Lancs, UK: Parthenon Pub. Group, 1990.

Знайти повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Luiten, Rosalie Margaretha. New chimeric monoclonal antibodies against human carcinomas: IgE and bispecific antibody-mediated therapy. [Leiden: University of Leiden, 1998.

Знайти повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Gray, Lynn. Dynamic antibody industry, including polyclonals and monoclonals. Norwalk, CT: Business Communications Co., 2002.

Знайти повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Magerstadt, Michael. Antibody conjugates and malignant disease. Boca Raton: CRC Press, 1991.

Знайти повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

W, Baldwin R., Byers Vera S, and Mann R. D. 1928-, eds. Monoclonal antibodies and immunoconjugates in cancer treatment. Carnforth: Parthenon Publishing, 1990.

Знайти повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Rotheim, Philip. The dynamic antibody industry, including polyclonals and monoclonals. Norwalk, CT: Business Communications Co., 1992.

Знайти повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Більше джерел

Частини книг з теми "Monoclonal antibody, immunocytokine, immunotherapy"

Mittendorf, Elizabeth A., and Sabitha Prabhakaran. "Monoclonal Antibody Therapy." In Immunotherapy in Translational Cancer Research, 12–23. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2018. http://dx.doi.org/10.1002/9781118684535.ch2.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Borghaei, Hossein, Matthew K. Robinson, and Louis M. Weiner. "Monoclonal Antibody Therapy of Cancer." In Immunotherapy of Cancer, 487–502. Totowa, NJ: Humana Press, 2006. http://dx.doi.org/10.1385/1-59745-011-1:487.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Gray, Juliet C., and Paul M. Sondel. "Overview of Monoclonal Antibody Therapies." In Immunotherapy for Pediatric Malignancies, 65–78. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-43486-5_4.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Rader, Christoph. "Monoclonal Antibody Therapy for Cancer." In Experimental and Applied Immunotherapy, 59–83. Totowa, NJ: Humana Press, 2010. http://dx.doi.org/10.1007/978-1-60761-980-2_3.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Hamblin, T. J. "Modifications of Monoclonal Antibody for Immunotherapy." In Immunotherapy of Disease, 143–66. Dordrecht: Springer Netherlands, 1989. http://dx.doi.org/10.1007/978-94-009-1844-3_7.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Pescovitz, Mark D. "Rituximab, an Anti-CD20 Monoclonal Antibody." In Immunotherapy in Transplantation, 362–77. Oxford, UK: Wiley-Blackwell, 2012. http://dx.doi.org/10.1002/9781444355628.ch24.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Embleton, M. J., and R. W. Baldwin. "MONOCLONAL ANTIBODY TARGETING FOR CANCER IMMUNOTHERAPY." In Proceedings of the Third Symposium, Lyon, France, June 26–28, 1985, edited by Jacques Bienvenu, J. A. Grimaud, and Philippe Laurent, 529–42. Berlin, Boston: De Gruyter, 1986. http://dx.doi.org/10.1515/9783110860757-066.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Gouda, Gayatri, Manoj Kumar Gupta, Ravindra Donde, Lambodar Behera, and Ramakrishna Vadde. "Monoclonal Antibody Therapy Against Gastrointestinal Tract Cancers." In Immunotherapy for Gastrointestinal Malignancies, 97–111. Singapore: Springer Singapore, 2020. http://dx.doi.org/10.1007/978-981-15-6487-1_7.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Reisfeld, R. A. "Immunotherapy of Melanoma with Monoclonal Antibody-Drug Conjugates." In Human Melanoma, 399–412. Berlin, Heidelberg: Springer Berlin Heidelberg, 1990. http://dx.doi.org/10.1007/978-3-642-74496-9_28.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Masuho, Yasuhiko, Yoh-Ichi Matsumoto, Tohru Sugano, Takami Tomiyama, Satoshi Sasaki, and Tamotsu Koyama. "Development of a Human Monoclonal Antibody against Cytomegalovirus with the Aim of a Passive Immunotherapy." In Therapeutic Monoclonal Antibodies, 187–207. London: Palgrave Macmillan UK, 1990. http://dx.doi.org/10.1007/978-1-349-11894-6_12.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Тези доповідей конференцій з теми "Monoclonal antibody, immunocytokine, immunotherapy"

Lin, Haishan, and Richard Zhang. "Abstract B73: Development of anti-human CLDN18.2 monoclonal antibody as cancer therapeutics." In Abstracts: AACR Special Conference on Tumor Immunology and Immunotherapy; November 27-30, 2018; Miami Beach, FL. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/2326-6074.tumimm18-b73.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Alrishedan, NS, W. Bodmer, V. Liebe lastun, V. Golubovskaya, J. Wu, A. Bransi, P. Umana, C. Klein, and R. Mateus Seidl. "P01.01 PLAP as target for cancer immunotherapy – development and preclinical characterization of bispecific monoclonal antibody in colorectal cancer immunotherapy." In iTOC9 – 9th Immunotherapy of Cancer Conference, September 22–24, 2022 – Munich, Germany. BMJ Publishing Group Ltd, 2022. http://dx.doi.org/10.1136/jitc-2022-itoc9.13.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Mick, Rosemarie, David Bajor, Lee Richman та Robert Vonderheide. "Abstract A10: Soluble CD25 and C-reactive protein predict overall survival in melanoma patients receiving anti-CD40 monoclonal antibody CP-870,893 (αCD40) and anti-CTLA4 monoclonal antibody tremelimumab". У Abstracts: AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/2326-6074.tumimm14-a10.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Welt, Rachel S., Jonathan A. Welt, Virginia Raymond, David Kostyal, and Sydney Welt. "Abstract PO020: Anti-membrane-IgM monoclonal antibody, mAb4, inhibits the BCRC, modulating downstream signaling pathways." In Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; October 19-20, 2020. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/2326-6074.tumimm20-po020.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Kim, Haemi, Kyoung-Jin Kim, Myeong Jin Yoon, Jenny Choih, Eun Ji Cho, Hak-Jun Jung, Kwanghyun Lee, et al. "488 GNUV201, a novel human and mouse cross-reactive PD-1 monoclonal antibody for cancer immunotherapy." In SITC 37th Annual Meeting (SITC 2022) Abstracts. BMJ Publishing Group Ltd, 2022. http://dx.doi.org/10.1136/jitc-2022-sitc2022.0488.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Salameh, Ahmad, Jerri Caldeira, Valeria Rolih, Elisabetta Bolli, Laura Conti, and Michael Perrine. "Abstract B37: Development of a monoclonal antibody targeting xCT/SLC7A11 expressed in metastatic cancer cells." In Abstracts: AACR Special Conference on Tumor Immunology and Immunotherapy; November 17-20, 2019; Boston, MA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/2326-6074.tumimm19-b37.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Macedo, Luciana F., Elizabeth Kaiser, Haiyan Jiang, Hillary Millar, Diana Wiley, Adam Cotty, Fred Kaplan, et al. "Abstract A190: Colon tumor cells expressing CD24 have oncogenic properties and are inhibited by monoclonal antibody immunotherapy." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Oct 19-23, 2013; Boston, MA. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1535-7163.targ-13-a190.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Mitsunaga, Makoto, Mikako Ogawa, Nobuyuki Kosaka, Peter L. Choyke, and Hisataka Kobayashi. "Abstract 3618: Target-specific photo-activatable immunotherapy (PIT) for cancer based on a monoclonal antibody-photosensitizer conjugate." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-3618.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Stecha, Pete, Denise Garvin, Julia Gilden, Jun Wang, Jamison Grailer, Jim Hartnett, Vanessa Ott, Frank Fan, Mei Cong, and Zhijie Jey Cheng. "Abstract 5658: A homogenous PBMC ADCC bioassay enables bridging studies with ADCC reporter bioassays in immunotherapy monoclonal antibody development." In Proceedings: AACR Annual Meeting 2020; April 27-28, 2020 and June 22-24, 2020; Philadelphia, PA. American Association for Cancer Research, 2020. http://dx.doi.org/10.1158/1538-7445.am2020-5658.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Stecha, Pete, Denise Garvin, Julia Gilden, Jun Wang, Jamison Grailer, Jim Hartnett, Gopal B. Krishnan, Frank Fan, Mei Cong, and Zhijie Jey Cheng. "Abstract 506: A homogenous PBMC ADCC bioassay enables bridging studies with ADCC reporter bioassays in immunotherapy monoclonal antibody development." In Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-506.

Повний текст джерела

Стилі APA, Harvard, Vancouver, ISO та ін.

Ми пропонуємо знижки на всі преміум-плани для авторів, чиї праці увійшли до тематичних добірок літератури. Зв'яжіться з нами, щоб отримати унікальний промокод!