Дисертації з теми "Antibody treatment"
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Alsughayyir, Jawaher. "CD49d-specific Single Domain Antibodies for the Treatment of Multiple Sclerosis." Thesis, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/23528.
Повний текст джерелаChen, Chao, and 陳超. "Identification of a novel cancer therapeutic antibody against human epidermal growth factor receptor 2 (Her2) and antibody engineering for development of cancer therapeutics." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/196461.
Повний текст джерелаpublished_or_final_version
Microbiology
Doctoral
Doctor of Philosophy
Schroeder, Krista Marie. "Disparities in Monoclonal Antibody Treatment of Elderly Metastatic Colorectal Cancer Patients." ScholarWorks, 2015. https://scholarworks.waldenu.edu/dissertations/1421.
Повний текст джерелаOdili, Joy Ifeyinewa. "Development of specific antibody fragments for the detection and treatment of melanoma." Thesis, University College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.430128.
Повний текст джерелаAlberts, Justin Charles John. "Bispecific antibody mediated targeting cytotoxic lymphocytes for the treatment of colorectal carcinoma." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248396.
Повний текст джерелаDouglass, Angela. "The use of an antibody in the diagnosis and treatment of liver fibrosis." Thesis, University of Aberdeen, 2009. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=131533.
Повний текст джерелаDI, CINTIO FEDERICA. "Nanoparticles anti-GPC1 for glioblastoma multiforme treatment." Doctoral thesis, Università degli Studi di Trieste, 2022. http://hdl.handle.net/11368/3015204.
Повний текст джерелаGlioblastoma multiforme (GBM) the most aggressive (WHO grade IV) diffuse glioma, is also by far the most frequent one. After standard treatment, the 2-year overall survival of GBM patients is approximately only 25%. Although numerous experimental drugs have been tested in clinical trials, GBM patients have not yet profited of curative treatments. To overcome the big limitations regarding GBM treatment, we address the challenge of developing a drug delivery system based on highly biocompatible chitosan nanobubbles (NBs) conjugated with an anti-glypican1 (GPC1) antibody loaded with docetaxel as chemotherapeutic agent. This drug delivery approach has been proposed to counter major challenges as overcoming the BBB, allowing the therapeutic release exclusively to tumor cells, and minimizing the possible side effects in cancer patients. The GPC1 proteoglycan has been chosen as useful target for drug delivering with NBs, therefore GPC1 expression was characterized in-vitro, being found expressed in GBM cell lines (e.g., T98G, U87-MG) but not found expressed in non-GBM cell line. Consistently, we assessed the localization of GPC1 protein expression on the cell surface and in the cytoplasm of GBM cell lines whereas it was lacked in the negative control cells. Of note, in primary tumor sections of these 10 GBM cases, GPC1 was found overexpressed whereas in normal tissues was found not expressed. To obtain a specific anti-GPC1 antibody recognizing the last 70 amino acid of GPC1 protein and therefore the cell-surface form of GPC1, mouse immunization has been performed. Hybridomas have produced three different anti-GPC1 specific clones (A, B, C). By using the B and C clones, GPC1 expression was detected in GBM cells at levels comparable to the levels obtained by using the commercially available antibody by the B and C clones. On the contrary, the A clone was not capable to recognize GPC1. Therefore, we purified the B and C clones to obtain specific anti-GPC1 monoclonal Abs. Moreover, C and B appeared to be more efficient than the a-GPC1c for detection of GPC1 expression levels. According to the results of antibody testing in GBM cell lines and negative control cell lines, the B clone was chosen to be conjugated to the NBs to develop the active drug delivery strategy. To select the drug to be loaded in the NBs, the killing capability of temozolomide (TMZ), paclitaxel (PTX) and docetaxel (DTX) was evaluated in GBM cells. DTX have the highest killing capability compared to PTX and TMZ. Therefore, we used DTX for the NBs loading encapsulation. The in-vitro characterization of NBs showed the average diameter of about 350 nm and a positive charge and spherical morphology. In-vitro analysis of the treatment of NBs in GBM cells, showed the localization of NBs conjugated with B antibody in cell cytoplasm around the nucleus. In contrast, a lower mean fluorescence intensity was observed for the cells treated with unconjugated NBs. For the in-vitro cytotoxic effect of NBs, NB loaded with DTX, NBs loaded with DTX and conjugated with B antibody, showed a killing capability correlated with the concentration in each evaluated point, with cell viable levels comparable to those of free DTX for some concentrations. Blank NBs, NB conjugated with Cy 5.5, and NB conjugated with B antibody were not toxic at all tested concentrations. In-vivo and ex-vivo test of the biodistribution of anti-GPC1 NBs in xenograft GBM mouse models, showed that the presence of the conjugation with the B antibody seems to be allow a major accumulation of the injected NBs in the tumor as well as a higher retention time at least until the last time point of 96 h of treatment. In conclusion, the proposed active drug delivery approach using anti-GPC1 conjugated NBs loaded with DTX could be useful for the treatment of GBM.
Arrowood, Michael James. "Cryptosporidium: Oocyst production and hybridoma generation for examining colostrum and monoclonal antibody roles in cryptosporidial infections." Diss., The University of Arizona, 1988. http://hdl.handle.net/10150/184335.
Повний текст джерелаLopez-Oliva, Santa Cruz Isabel. "Rheumatoid arthritis and periodontitis : antibody response, oral microbiome, cytokine profile and effect of periodontal treatment." Thesis, University of Birmingham, 2018. http://etheses.bham.ac.uk//id/eprint/8058/.
Повний текст джерелаLocker, Kathryn CS. "Molecular mechanisms underlying treatment of acute type 1 diabetes with an anti-TLR4/MD2 antibody." University of Cincinnati / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1601993060493285.
Повний текст джерелаWetzel, Hanna N. "Preclinical Development of the Anti-cocaine Monoclonal Antibody h2E2 for the Treatment of Cocaine Addiction." University of Cincinnati / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1529333855259163.
Повний текст джерелаLeung, Chieh-wing Jervis, and 梁倢榮. "Development of a real-time PCR-based method for the measurement of neutralizing antibody to interferon-beta in multiple sclerosis patients." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206488.
Повний текст джерелаpublished_or_final_version
Pathology
Master
Master of Medical Sciences
vanzolini, tania. "Development of new biological drugs for the treatment of fungal infections." Doctoral thesis, Urbino, 2021. http://hdl.handle.net/11576/2692691.
Повний текст джерелаLichvar, Alicia B. "Proteasome Inhibitor Treatment of Antibody Mediated Rejection and Mixed Acute Rejection: Defining Factors that Predict Long-Term Outcomes." University of Cincinnati / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1490698721411028.
Повний текст джерелаNonomura, Yumi. "Peripheral blood Th9 cells are a possible pharmacodynamic biomarker of nivolumab treatment efficacy in metastatic melanoma patients." 京都大学 (Kyoto University), 2017. http://hdl.handle.net/2433/225479.
Повний текст джерелаSartor, Chiara <1988>. "Research of predictive biomarkers to anti-CD22 antibody-drug conjugate treatment in B-cell acute lymphoblastic leukemia." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2022. http://amsdottorato.unibo.it/10252/1/PhD%20thesis_Chiara%20Sartor_XXXIV%20ciclo.pdf.
Повний текст джерелаMontanini, M. "ANTI-CD25 MONOCLONAL ANTIBODY (MAB):AN IMMUNOMODULATING DRUG CANDIDATE FOR THE TREATMENT OF T-CELL MEDIATED DISEASES." Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/245741.
Повний текст джерелаMATRICARDI, SARA. "Epileptic phenotypes, treatment options and long-term outcomes of autoimmune epilepsies." Doctoral thesis, Università Politecnica delle Marche, 2021. http://hdl.handle.net/11566/288143.
Повний текст джерелаBackground and aims Epileptic seizures may be a presenting or prominent symptom of brain dysfunction in autoimmune encephalitis. They are usually resistant to symptomatic therapy with antiseizure medications (ASMs) but may benefit from immunomodulatory treatments. Despite the increasing knowledge in this field and progress in research interest, autoimmune epilepsy is still an under-recognized condition without standardized diagnostic and management guidelines. This study aims to analyze the epileptic phenotypes of seizures of autoimmune etiology, assessing their clinical presentation, seizure semiology, and associated paraclinical findings. Treatment options, management, and overall outcomes at the long-term were also provided. Methods An observational cohort study was retrospectively performed over 10 years period (from 2010 to 2020). This is a nationwide study, carried out in 34 Italian epilepsy centers being part of the network of high expertise centers of the Italian League Against Epilepsy [LICE]. Patients with new-onset seizures of an autoimmune etiology were enrolled. This latter was defined by the detection of antineuronal antibodies or suspected on the basis of clinical presentation and paraclinical findings. Results Overall, 263 patients (138 females; median age 55 years, range 4-86) were enrolled and followed-up for a median time of 30 months (range 12-120). The median age at seizure onset was 48 years (range 2-82). Antineuronal antibodies were detected in 63.50% of cases (79.65% of them had antibodies targeting neuronal cell-surfaceantigens). No specific seizure semiology was found to be related to antibody-positivity, except for facio-brachial dystonic seizures, which are pathognomonic of LGI1 encephalitis (p< 0.001). Most antibody-positive patients had multiple seizure types (p=0.01); and a prevalent involvement of the temporal regions (p=0.02), but when performing the multivariate analysis, these features were not confirmed to be independent predictors for antibody detection. Of interest, a higher prevalence of episodes of statusepilepticus was found in the antibody-negative patients (OR 0.23, 95% CI 0.12-0.45; p<0.001), which also usually leads to a less favorable prognosis in these cases.During the acute phase, 87.73% presented seizures drug-resistant to most common ASMs, without any significant prevalence in antibody detection. Besides seizures, the acute phase was also marked by associated symptoms in 93%; mostly cognitive impairment, psychiatric symptoms, and sleep disorders were prevalent in antibody-positive subgroup (OR 4.70, 95% CI 2.33-9.47; OR 3.43, 95% CI 1.81-6.50; OR 5.41, 95% CI 2.16-13.52, respectively; p< 0.001). Most patients (88.60%) were treated with immunotherapy, and 61.80% of them were considered responders. Independent predictors of a favorable outcome were confirmed to be early immunotherapy (within 3 months from the onset; OR 12.08, 95% CI 5.50-26.50; p<0.001) and the detection of antineuronal surface antibodies (OR 2.38; 95% CI 1.15-4.92; p=0.01). Long-term outcomes were marked by persisting seizures beyond the acute phase of the encephalitis in 43.73%, with a prevalence in antibody-negative patients (p<0.001), associated with neuropsychological deficits and psychiatric disorders in81.73% of them. Conclusions The increasing recognition of an autoimmune basis of epilepsies and the broad spectrum of autoimmune encephalitis with predominant epileptic seizures has raised interest in scientific and clinical epileptology, opening a new field with challenging issues in diagnosis and treatment. The comparison between subgroups of antibody findings and outcomes may improve the operative definition and characterization. An autoimmune etiology represents a rare chance in seizures management, and an early treatment at the pathogenic level may reduce the risk of irreversible sequelae at the long-term. This study provides Class IV evidence for management recommendations.
Hänel, Mathias, Friedrich Fiedler, and Christoph Thorns. "Anti-CD20 Monoclonal Antibody (Rituximab) and Cidofovir as Successful Treatment of an EBV-Associated Lymphoma with CNS Involvement." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-135105.
Повний текст джерелаHintergrund: Die Epstein-Barr-Virus(EBV)-assoziierte Posttransplantations-lymphoproliferative Disease (PTLD) ist eine gefürchtete Komplikation nach allogener hämatopoetischer Stammzelltransplantation (HSCT). Insbesondere bei Befall des zentralen Nervensystems (ZNS) ist die Behandlung auf Grund der unsicheren Liquorwirksamkeit der meisten Chemotherapeutika als auch von EBV-spezifischen zytotoxischen T-Spenderzellen schwierig. Der monoklonale Anti-CD20-Antikörper Rituximab wurde in den letzten Jahren bei Patienten mit EBV-PTLD intensiv untersucht. Allerdings wurde bislang lediglich von 8 Patienten mit ZNS-Befall eines B-Zell-Lymphoms berichtet, bei denen eine Therapie mit Rituximab erfolgte. Kasuistik: Eine 24-jährige Patientin hatte wegen einer akuten T-lymphoblastischen Leukämie in zweiter kompletter Remission eine allogen-unverwandte, T-Zelldepletierte HSCT erhalten. 10 Monate später wurde eine EBV-assoziierte PTLD diagnostiziert. Neben peripheren Lymphomen und B-Symptomen zeigte die Patientin neurologische Symptome. Die Liquoruntersuchung erbrachte den Befund einer Meningeosis lymphoblastica im Rahmen des EBV-Lymphoms. Die Behandlung mit Rituximab und dem Virustatikum Cidofovir führte zu einer kompletten Remission mit Rückbildung der peripheren Lymphome und Verschwinden der neurologischen Symptomatik. Außerdem wurde die PCR-Kontrolle auf EBV-DNA sowohl im Plasma als auch im Liquor negativ. Schlussfolgerung: Die Kombination von Rituximab und Cidofovir erscheint als eine interessante Therapiealternative für Patienten mit EBV-assoziierter PTLD und ZNS-Befall
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
Wareham, Carol. "Exploring the efficacy of anti-GD2 and anti-4-1BB monoclonal antibody therapy for the treatment of neuroblastoma." Thesis, University of Southampton, 2014. https://eprints.soton.ac.uk/376894/.
Повний текст джерелаHänel, Mathias, Friedrich Fiedler, and Christoph Thorns. "Anti-CD20 Monoclonal Antibody (Rituximab) and Cidofovir as Successful Treatment of an EBV-Associated Lymphoma with CNS Involvement." Karger, 2001. https://tud.qucosa.de/id/qucosa%3A27618.
Повний текст джерелаHintergrund: Die Epstein-Barr-Virus(EBV)-assoziierte Posttransplantations-lymphoproliferative Disease (PTLD) ist eine gefürchtete Komplikation nach allogener hämatopoetischer Stammzelltransplantation (HSCT). Insbesondere bei Befall des zentralen Nervensystems (ZNS) ist die Behandlung auf Grund der unsicheren Liquorwirksamkeit der meisten Chemotherapeutika als auch von EBV-spezifischen zytotoxischen T-Spenderzellen schwierig. Der monoklonale Anti-CD20-Antikörper Rituximab wurde in den letzten Jahren bei Patienten mit EBV-PTLD intensiv untersucht. Allerdings wurde bislang lediglich von 8 Patienten mit ZNS-Befall eines B-Zell-Lymphoms berichtet, bei denen eine Therapie mit Rituximab erfolgte. Kasuistik: Eine 24-jährige Patientin hatte wegen einer akuten T-lymphoblastischen Leukämie in zweiter kompletter Remission eine allogen-unverwandte, T-Zelldepletierte HSCT erhalten. 10 Monate später wurde eine EBV-assoziierte PTLD diagnostiziert. Neben peripheren Lymphomen und B-Symptomen zeigte die Patientin neurologische Symptome. Die Liquoruntersuchung erbrachte den Befund einer Meningeosis lymphoblastica im Rahmen des EBV-Lymphoms. Die Behandlung mit Rituximab und dem Virustatikum Cidofovir führte zu einer kompletten Remission mit Rückbildung der peripheren Lymphome und Verschwinden der neurologischen Symptomatik. Außerdem wurde die PCR-Kontrolle auf EBV-DNA sowohl im Plasma als auch im Liquor negativ. Schlussfolgerung: Die Kombination von Rituximab und Cidofovir erscheint als eine interessante Therapiealternative für Patienten mit EBV-assoziierter PTLD und ZNS-Befall.
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
Kao, Daniel Joseph. "Development of a synthetic peptide vaccine and antibody therapeutic for the prevention and treatment of Pseudomonas Aeruginosa infection /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.
Знайти повний текст джерелаTypescript. Includes bibliographical references (leaves 203-212; 260-261). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;
Rahnama, Samira. "The development of a novel treatment for equine laminitis." Thesis, Queensland University of Technology, 2020. https://eprints.qut.edu.au/199907/1/Samira_Rahnama_Thesis.pdf.
Повний текст джерелаHu, Eileen Yifan. "Developing Methods and Targeted Therapeutics to Address Complications of Ibrutinib Treatment in Chronic Lymphocytic Leukemia." The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1587494624201361.
Повний текст джерелаMcBride, Harry Michael. "The recruitment of ribosomal inactivating protein or T cells by antibody derivatives in the treatment of B cell lymphoma." Thesis, University of Southampton, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295851.
Повний текст джерелаBarbarino, Verena [Verfasser], Christian [Gutachter] Pallasch, and Marcus [Gutachter] Krüger. "Macrophage-mediated antibody dependent effector function in aggressive B cell lymphoma treatment / Verena Barbarino ; Gutachter: Christian Pallasch, Marcus Krüger." Köln : Universitäts- und Stadtbibliothek Köln, 2021. http://nbn-resolving.de/urn:nbn:de:hbz:38-531485.
Повний текст джерелаJayaram, Rohith. "A Local, Sustained Delivery System for Zoledronic Acid and RANKL-Inhibitory Antibody as a Potential Treatment for Metastatic Bone Disease." UKnowledge, 2015. http://uknowledge.uky.edu/cbme_etds/34.
Повний текст джерелаOden, Felix [Verfasser]. "Generation of an antibody targeting B cell maturation antigen for the treatment of multiple myeloma and autoimmune diseases / Felix Oden." Berlin : Freie Universität Berlin, 2014. http://d-nb.info/1063934494/34.
Повний текст джерелаIshida, Yoshihiro. "Killer immunoglobulin-like receptor genotype did not correlate with response to anti-PD-1 antibody treatment in a Japanese cohort." Kyoto University, 2020. http://hdl.handle.net/2433/253207.
Повний текст джерелаAkgün, Katja, Imke Metz, Hagen H. Kitzler, Wolfgang Brück, and Tjalf Ziemssen. "Rescue therapy with alemtuzumab in B cell/antibody-mediated multiple sclerosis." Sage, 2018. https://tud.qucosa.de/id/qucosa%3A35543.
Повний текст джерелаHaack, Stephanie [Verfasser], and Niklas [Gutachter] Beyersdorf. "A novel mouse model for systemic cytokine release upon treatment with a superagonistic anti-CD28 antibody / Stephanie Haack ; Gutachter: Niklas Beyersdorf." Würzburg : Universität Würzburg, 2021. http://d-nb.info/123439152X/34.
Повний текст джерелаJohansson, Jeannette. "Antibodies for better or worse or Antibody variability in an egg-laying mammal and a novel strategy in the treatment of allergies." Doctoral thesis, Uppsala University, Department of Cell and Molecular Biology, 2002. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2533.
Повний текст джерелаAntibodies are a central part of the immune defense system, and a large variability in their specificity is needed in order to be able to react against all possible foreign substances we may encounter during our lives. In this thesis, results are presented from investigations into how an egg-laying mammal, the Australian duck-billed platypus (Ornithorhynchus anatinus) creates antibody variability. Our results show that despite the lack of many V gene families the antibody repertoire in the platypus seems to be well developed. A long and highly variable complementarity-determining region (CDR) 3 compensates for the limited germline diversity. Interestingly, the presence of additional cysteine residues in the CDRs may form stabilizing disulfide bridges in the antigen binding loops and thereby increasing the affinity of the antibody-antigen interaction.
Although the immune system is necessary for survival, it must be strictly controlled since it may otherwise over-react and cause more harm than benefits. Allergies and autoimmune diseases are examples of such over-reactions by the immune system. Allergies are increasing in the western world and have become one of the main medical issues of the 21st century. IgE is the central mediator in atopic allergies such as hay fever, eczema and asthma; it is therefore a prime target in the development of allergen-independent preventative treatments. Here we present results from several studies of a novel vaccine strategy aimed at reducing the levels of IgE antibodies. The vaccine results in the induction of anti-IgE antibodies, and the skin reactivity upon allergen challenge was significantly reduced in vaccinated animals. Our results suggest that active immunization against IgE has the potential to become a therapeutic method for humans. In addition, an evaluation of possible adjuvants that could be used as immune stimulators and thus help break self-tolerance at the time of vaccination is presented.
Marckel, Jordan A. "The in-vivo Preclinical Development of a Humanized Anti-cocaine Monoclonal Antibody and its Fab Fragment for the Treatment of Cocaine Abuse." University of Cincinnati / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1613745458699203.
Повний текст джерелаNicolay, Uwe. "Health-related quality of life, treatment satisfaction and clinical aspects of patients with primary antibody deficiency receiving subcutaneous IgG self-infusions at home /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-826-6/.
Повний текст джерелаSantos, Filipe Miguel Barão dos. "Canine lymphoma immunophenotype prevalence and predisposition and evaluation of SN38 to be used in an antibody-drug conjugate for B-cell lymphoma treatment." Master's thesis, Universidade de Lisboa, Faculdade de Medicina Veterinária, 2021. http://hdl.handle.net/10400.5/21061.
Повний текст джерелаLymphoma is one of the most diagnosed neoplasias in dogs and one of the most recurring in clinical practice. This disease features various immunophenotypes, clinical and anatomopathological presentations, being the B-cell lymphoma the most reported in literature. In this species, lymphoma is similar to non-Hodgkin human lymphoma regarding therapy response, immunophenotype and anatomopathological presentation. Therefore, the dog is a very good spontaneous model for comparative studies. In this way, a statistical study was conducted in order to investigate the frequency for each immunophenotype and a possible breed predisposition for them, in comparison with previous studies. The sample included 165 records of canine lymphoma cases from 36 breeds kept by the Laboratory of Pathological Anatomy of the Faculty of Veterinary Medicine in the last 7 years with an immunohistochemistry diagnosis. Hitherto, conventional therapy comprises chemotherapy, corticotherapy and radiotherapy. However, these approaches have their limitations. This arises the need for novel therapies. Amongst those, immunotherapy with antibody-drug conjugates (ADCs) stands out since they allow for a more specific and directed therapy with less side effects. Given the promising potential of these strategies, the aim of this project consisted in contributing to the development of an ADC through the cloning of previously selected single-domain antibodies (sdAbs) in a pET21a vector for large-scale production and the validation of SN38 as a cytotoxic drug to link to these antibodies. The final aim was the ADC therapeutic application in canine B-cell lymphoma. Making use of descriptive statistics and Fisher’s exact tests, the obtained results confirmed a large majority of B-cell lymphoma cases (72.7%) but, contrarily to previous studies, an association with lymphoma immunophenotype was not found in the majority of the studied breeds. These results are not very statistically reliable, due to the small sample population. The cell viability assays performed with SN38 in two B-cell lymphoma lines, a canine lymphoma (CLBL-1) and a human lymphoma cell line (Raji), disclosed IC50 ranging between 4 to 300 nM, promising results which reinforce the importance in investing in more studies in order to obtain more data that can validate this compound for canine lymphoma therapy.
ABSTRACT - Predisposição e prevalência de imunofenótipos do linfoma canino e avaliação do SN38 para utilização num imunoconjugado para tratamento do linfoma de células B - O linfoma é uma das neoplasias mais diagnosticada em cães e uma das mais recorrentes na prática clínica. Esta doença apresenta vários imunofenótipos e apresentações clínicas e anatomopatológicas, sendo o linfoma de células B o mais registado na literatura. Nesta espécie, o linfoma assemelha-se ao linfoma não-Hodgkin no Homem, nomeadamente na resposta à terapia, imunofenótipo e apresentação anatomopatológica. Assim, o cão apresenta-se como um excelente modelo espontâneo de estudos comparativos com o Homem. Desta forma, foi efectuado um estudo estatístico de forma a averiguar a frequência de cada imunofenótipo e uma possível predisposição de raça para os mesmos em comparação com estudos anteriores. A amostra incluiu 165 registos de casos de linfoma canino de 36 raças mantidos pelo Laboratório de Anatomia Patológica da Faculdade de Medicina Veterinária nos últimos 7 anos com diagnóstico imunohistoquímico. Até à data, a terapêutica convencional para o linfoma resume-se à terapêutica com anti-neoplásicos, à corticoterapia e à radioterapia. Contudo, estas abordagens têm limitações. Atendendo a estas adversidades, surge a necessidade de novas terapias. Destas, destaca-se a imunoterapia com anticorpos conjugados com fármacos citotóxicos (ADCs) que permitem uma terapia mais específica e direccionada, com menos efeitos adversos. Dado o potencial promissor destas estratégias, este trabalho teve como objectivo contribuir para o desenvolvimento de um ADC através da clonagem de anticorpos de domínio único (sdAbs), previamente seleccionados, num vector pET21a para produção em larga escala e validação do SN38 como composto citotóxico para ligação a estes anticorpos, tendo em vista a sua aplicação terapêutica em linfoma canino de células B. Com recurso a estatística descritiva e testes exactos de Fisher, os resultados obtidos confirmaram uma larga maioria de casos de linfoma de células B (72,7%), mas, contrariamente a estudos prévios, não se encontrou uma associação com imunofenótipo na maioria das raças estudadas, resultados estes estatisticamente pouco significativos devido à pequena amostra do estudo. Os ensaios de viabilidade celular realizados com o SN38 em duas linhas celulares de linfoma de células B, uma de linfoma canino (CLBL-1) e outra de linfoma humano (Raji), revelaram valores de IC50 na ordem dos 4 a 300 nM, resultados promissores que reforçam a importância de investir em mais estudos de forma a obter mais dados que possibilitem validar este composto na terapêutica do linfoma canino.
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Caudana, Pamela. "Translating IL-2/anti-IL-2 antibody complexes treatment for human tumor immunotherapy IL-2/anti-IL-2 antibody complex combined with CTLA-4- but not PD1- blockade rescues anti-tumor NK function by modulating intra-tumoral regulatory T cells." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCB146.
Повний текст джерелаHigh-dose IL-2 was the first immunotherapy ever assessed for the treatment of human cancer, achieving similar objective responses in metastatic melanoma as with a-checkpoint mAbs treatment (15%). However, less than 10% of eligible patients receive this potentially curative treatment, likely due to its associated toxicity and need of hospitalization, as well as concern on the expansion of Treg cells. Consequently, different approaches have been applied to bring back IL-2 to the clinics, trying to bypass Treg activation and to improve IL-2 pharmacodynamics. One of these strategies is the use of IL-2/anti-IL-2 mAb complexes (IL-2Cx). In mouse studies it has been shown that when IL-2 is complexed with an anti-IL-2 antibody (Ab), IL-2 pharmacodynamics is improved, toxicity is lowered and depending on the Ab, the IL-2Cx can direct IL-2 action to effector or to regulatory immune cells. In the past years, Treg-stimulating IL-2Cx have been successfully used in preclinical models of autoimmune diseases like EAE, Arthritis, renal diseases and allergy. On the other hand, effector cell-stimulating IL-2Cx have shown to delay tumor growth in preclinical models of melanoma, leukemia and renal cell carcinoma. Heretofore, all published preclinical data have been obtained using IL-2Cx formed with commercial rat anti-mouse IL-2 or rat-anti human IL-2 Abs, but yet, there are no available IL-2Cx formed with clinical-grade anti-human (h) IL-2 mAbs. In this context, my thesis work was dedicated to: i) the generation of human anti-human IL-2 Abs that when complexed with hIL-2 preferentially activate NK and effector CD8+ T cell, for cancer treatment; and ii) the pre-clinical evaluation of the efficacy of combinatory treatments using IL-2Cx with immunecheckpoint (CKP) blockade for cancer therapy. To generate human anti- hIL-2 Abs we used two strategies: i) phage display against hIL-2 using a pre-immune lama library; and ii) isolation of anti-hIL-2 auto-antibodies from B cells obtained from Type 1 diabetic patients, previously described by our team. Using both techniques, we succeeded in generating large amounts of anti-hIL-2 Abs, but we encountered many difficulties to isolate those with the desired IL-2Cx activity. To solve this technical issue, in collaboration with a team at Institut Pasteur in Paris, we designed new hIL-2 variants allowing a simplified screening of the IL-2 Abs (currently under patenting process). In parallel, we evaluated the anti-tumoral efficacy of effector cell-stimulating IL-2Cx combined with blockade of CTLA-4 and PD1 pathway, with a translational perspective. First, in an inducible spontaneous lung adenocarcinoma model we showed that the IL-2Cx/anti-PD1 combo durably controlled tumor growth and induced tumor-specific T cell responses. In the B16-OVA syngeneic model, naturally resistant to anti-checkpoint inhibition, combination of IL-2Cx with PD1 or CTLA-4 pathway blockade reversed resistance. Mechanistically, both combos worked by re-invigorating intratumoral CD8+ T cells and increasing the breath of tumor-specific T cell responses. However, only the IL-2Cx/anti-CTLA-4 combo diminished intratumoral Treg cells, leading to an increase in the NK/Treg cell ratio and is non-redundantly dependent on NK cells. No treatment toxicity was observed when IL-2 was used in the form of IL-2Cx. Overall, our results suggest that IL-2-based therapies should be reconsidered for the treatment of cancer. Moreover, our observation that the combinations of IL-2Cx with PD1 or CTLA-4 pathway blockade act by different cellular mechanisms, paves the way for the rational design of combinatorial anti-tumoral therapies
Buteyn, Nathaniel J. "Role of Innate Immunity Activators in the Treatment of Acute Myeloid Leukemia." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1574343556916953.
Повний текст джерелаAnzicek, Nika. "Studies towards a second-generation synthesis of the aplyronines." Thesis, University of Cambridge, 2017. https://www.repository.cam.ac.uk/handle/1810/267831.
Повний текст джерелаDias, Joana Nunes Ribeiro. "Clinical and immunological characterization of naturally occurring canine lymphoma : development and application of engineered recombinant antibodies for diagnosis and treatment." Doctoral thesis, Universidade de Lisboa, Faculdade de Medicina Veterinária, 2019. http://hdl.handle.net/10400.5/17735.
Повний текст джерелаNon-Hodgkin lymphoma (NHL) is one of the most common causes of cancer-related death worldwide. Although the outcome of NHL patients has improved with current therapies, the rate of mortality is still high. A plethora of new drugs is entering clinical development for NHL treatment; however, the approval of new treatments remains low due in part to the paucity of clinically relevant models for validation. Canine lymphoma (cNHL) shares remarkable similarities with its human counterpart, making the dog an excellent animal model to explore novel therapeutic options. Therefore, driven by the great success achieved by immunotherapies in human NHL, comparative research has focused on the development of similar immunotherapeutic approaches for dogs. However, the successful use of this animal model remains challenging, still lacking the characterization of the canine immune system, of common tumor epitopes, the development of canine-specific/cross-reactive agents and the establishment of preclinical models. Within this context, we aimed to develop novel antibody-based therapies for cNHL, while contributing for the characterization and validation of the cNHL model for translational immune-oncology research. For that purpose, a cNHL biobank was successfully constructed. The clinical cytokine patterns in patients with cNHL were investigated, confirming a local and systemic dysregulation in cytokine response. Furthermore, a positive correlation between intratumoral immune response and a favorable response to chemotherapy indicates that the modulation of the immune response might contribute to improve patient outcomes. With that in mind, a through characterization of canine CD20 expression was conducted and contributed for the validation of this receptor as a potential immunotherapeutic target for cNHL. This motivated the development and identification of a panel of single domain antibodies (sdAbs) with high binding activity and specificity to canine and human CD20. In addition, to develop a novel drug delivery system for cNHL treatment, we described novel methodologies to identify potential targets, while selecting highly specific sdAbs against NHL. This work allowed to select a promising pool of sdAbs that specifically target NHL tumor receptors for the development of a novel antibody drug conjugate (ADC). Furthermore, we conducted a thorough investigation of a novel ADC payload – panobinostat - a potent histone deacetylase (HDAC) inhibitor with strong in vitro and in vivo antitumor properties in cNHL. Finally, we established a new bioluminescent murine model for monitoring tumor progression and treatment response in preclinical studies. In summary, the work presented herein allowed the establishment of a solid platform for the acceleration of the translational research of novel immunotherapeutic approaches for comparative oncology.
RESUMO - Caracterização clínica e imunológica do linfoma canino como modelo animal : desenvolvimento de anticorpos recombinantes para tratamento e diagnóstico - O linfoma não-Hodgkin (LNH) é uma das principais causas de morte por neoplasia em todo o mundo, representando 90% de todos os linfomas. O LNH abrange um grupo heterogéneo de tumores, caracterizado pela proliferação de linfócitos malignos, 85-90% dos quais de linfócitos B. Os anticorpos direccionados para o recetor CD20, combinados com quimioterapias convencionais revolucionaram o tratamento do linfoma de células B, melhorando o tempo de remissão e aumentando a taxa de sobrevivência. No entanto, independentemente da terapêutica utilizada, a taxa de mortalidade mantém-se elevada. Uma grande diversidade de novos fármacos encontra-se em fase de desenvolvimento clínico para o tratamento do LNH; no entanto, a aprovação de novos tratamentos permanece baixa devido, em parte, à escassez de modelos clinicamente relevantes para validação. O cLNH e o LNH humano (hLNH) partilham muitas características histopatológicas, moleculares, genéticas e clínicas, desta forma o cão é considerado um excelente modelo animal para explorar novas opções terapêuticas. Consequentemente, a investigação em oncologia comparativa, motivada pelo grande sucesso alcançado pelas imunoterapias no tratamento do hLNH, tem-se focado no desenvolvimento de abordagens imunoterapêuticas semelhantes para cães. Contudo, o sucesso do cLNH como modelo animal tem vindo a revelar-se desafiante, na medida que a validação do seu uso para o desenvolvimento de imunoterapias ainda carece da caracterização do sistema imune canino, das células imunitárias e das moléculas efectoras, da avaliação dos epítopos tumorais comuns, do desenvolvimento de agentes imunoterapêuticos específicos para a espécie canina com potencial reacção cruzada com a espécie humana e do estabelecimento de modelos pré-clínicos para oncologia veterinária. Neste contexto, o presente trabalho teve como principal objectivo validar o cLNH como modelo animal para o desenvolvimento de novas estratégias imunoterapêuticas para LNH, visando estabelecer uma linha de investigação inovadora para o desenvolvimento de anticorpos recombinantes para o tratamento do cLNH. Neste sentido, desenvolveu-se uma estratégia multidisciplinar constituída por etapas complementares de modo a construir uma sólida plataforma para o desenvolvimento de ensaios clínicos de imunoterapias em oncologia comparativa...
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Setoyama, Takeshi. "Development of novel bioassay for the measurement of bioactive insulin-like growth factors in blood samples and treatment strategy targeting the bioactive insulin-like growth factors for non-islet cell tumor hypoglycemia." Kyoto University, 2016. http://hdl.handle.net/2433/204576.
Повний текст джерелаLind, Anne-Li. "Biomarkers for Better Understanding of the Pathophysiology and Treatment of Chronic Pain : Investigations of Human Biofluids." Doctoral thesis, Uppsala universitet, Anestesiologi och intensivvård, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-326180.
Повний текст джерелаUppsala Berzelii Technology Centre for Neurodiagnostics
Ferrière, Stephen. "Etude du mode d'action d’agents contournant l'action du facteur VIII dans l’hémophilie A Antibodies in the Treatment of Haemophilia A-A Biochemical Perspective A single-domaine antibody that blocks factor VIIa activity in the absence but not presence of tissue factor A hemophilia A mouse model for the in vivo assessment of emicizumab function." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASQ017.
Повний текст джерелаHemophilia A is a hemorrhagic disorder linked to the functional deficiency of coagulation factor VIII (FVIII). Clinical management of hemophilia A mostly relies on substitution therapy using FVIII concentrates. However, since patients may develop inhibitory antibodies against FVIII, alternative treatment strategies are required that bypass FVIII function, such as the use of recombinant Factor VIIa (rFVIIa) or a bispecific antibody that mimics FVIII activity, emicizumab. The aim of this thesis was to study the mode of action of both FVIII-bypassing therapeutics using novel, innovative tools specifically designed for this purpose. Although rFVIIa is clinically efficient, its mode of action was still unclear at the start of my studies. In a first part of this thesis, we have studied the mode of action of rFVIIa using a novel single-domain antibody (nanobody) that we generated and characterized. We first established that this nanobody, designated KB-FVIIa-004, inhibits FVIIa activity selectively in the absence but not presence of its cofactor, tissue factor (TF). This unique characteristic allowed us to show the the in vivo activity of rFVIIa is predominantly independent of its cofactor TF. In a second part of the study, we have examined the in vivo mode of action of the FVIII-mimetic emicizumab. Indeed, to measure its efficacy and equivalence to FVIII using in vitro assays is complicated and will generate inaccurate data. We therefore developed an innovative semi-humanized mouse model for hemophilia A, in which infused human factors IX and X. We were able to establish a FVIII-like activity of emicizumab (for a dose ≥1,5 mg/kg) corresponding to FVII dose of 4,5 U/kg (i.e. 9,0 U/dL). Interestingly, combining a low dose of FVIII (5 U/kg) with emicizumab resulted in a complete correction of the bleeding in our mouse model, suggesting an additive effect between FVIII and emicizumab
Chakraborti, Srinjoy. "Therapeutic Antibody Against Neisseria gonorrhoeae Lipooligosaccharide, a Phase-variable Virulence Factor." eScholarship@UMMS, 2017. https://escholarship.umassmed.edu/gsbs_diss/905.
Повний текст джерелаChakraborti, Srinjoy. "Therapeutic Antibody Against Neisseria gonorrhoeae Lipooligosaccharide, a Phase-variable Virulence Factor." eScholarship@UMMS, 2005. http://escholarship.umassmed.edu/gsbs_diss/905.
Повний текст джерелаMaho, Maud. "Evaluation des effets des traitements par Rituximab versus corticothérapie seule sur la réponse auto-réactive des patients atteints de pemphigus. First-line Rituximab combined with short-term Prednisone versus Prednisone alone for the treatment of Pemphigus (RITUX 3) : a prospective, multicentre, parallel-group, open-label randomised trial Risk factors for short-term relapse in patients with pemphigus treated by Rituximab as first-line therapy Rituximab and corticosteroid effect on Desmoglein specific B cells and T follicular helper cells in patients with Pemphigus Modifications or the transcriptomic profile of autoreactive B cells from pemphigus patients after treatment with Rituximab or standard corticosteroid regimen Long-term increase of Kcnn4 potassium channel surface expression on B cells in pemphigus patients after Rituximab treatment Rituximab is an effective treatment in patients with Pemphigus Vulgaris and demonstrates a steroid-sparing effect Modifications of the BAFF/BAFF-Receptor axis in patients with pemphigus treated with rituximab versus standard corticosteroids regimen. CD11C+ B cells are mainly memory cells prone to differentiate into antibody-secreting cells." Thesis, Normandie, 2019. http://www.theses.fr/2019NORMR132.
Повний текст джерелаPemphigus is an autoimmune disease of the skin and mucous membranes caused by autoantibodies (Ab) specific to desmoglein (Dsg) 1 or 3. These pathogenic Ab inhibit cell adhesion of keratinocytes. The development of pemphigus is associated with the conjunction of many uncommon events involving the emergence and then the cooperation of auto-reactive B cells and T cells link to genetic and environmental factors. Until now, the first line of treatment consisted of high doses of corticosteroids. Rituximab (RTX), an anti-CD20 chimeric monoclonal antibody, is an innovative therapy that results in B cells depletion. The RITUX 3 clinical trial was designed to evaluate the efficacy and safety of RTX combined with a short-course glucocorticoid therapy as a first-line treatment of pemphigus versus the standard treatment with standard corticosteroids (CS). As a first step, our clinico-biological analysis of patients after 24 months has shown that the use of RTX combined with short-term prednisone as a first-line treatment in patients with moderate to severe pemphigus is both more effective and better tolerated than the reference treatment with prednisone alone. Respectively, 89% of patients versus 34% in each group and both pemphigus foliaceus and pemphigus vulgaris patients responded. This efficacy was confirmed in the longer term after reconstitution of the B lymphocyte repertoire with a risk of relapse of only 2% at 36 months. The presence of a severe form of pemphigus at diagnosis (PDAI ≥ 45) and an anti-Dsg Ab level at 3 months above threshold values (anti-DSG1 ≥ 20 or anti-DSG3 ≥ 120) are associated with 50% risk of early relapse. These two predictive factors make it possible to identify a subgroup of patients at high risk of relapse requiring a maintenance infusion of RTX at the 6th month. In a second step, we studied the impact of RTX and CS treatments in patients with pemphigus in order to better understand the autoimmune response. The phenotypic characterization of auto-reactive B cells and the analysis of the frequency of B cells able of secreting anti-Dsg immunoglobulin (Ig) G by an ELISPOT approach demonstrated that the efficacy of RTX treatment in pemphigus seems related to the elimination of IgG-switched Dsg memory B-cells. Dsg specific B cells remain detectable after RTX when B cells return, but these B cells have a naïve and non-switched (IgM) phenotype and no longer secrete IgG. On the other hand, the persistence of self-reactive Dsg B cells capable of secreting IgG anti-Dsg after treatment with CS is certainly at the origin of the frequency of relapses. The unicellular targeted gene expression analysis demonstrated that initially, Dsg-specific B cells have a pro-inflammatory profile with the overexpression of three genes encoding Interleukin (IL) -1β, IL-12p35 and IL-23p19 and for the IRF5 gene (Interferon regulatory factor 5) compared to non-self-reactive B cells. RTX and CS have different effects on the expression of these genes, but both reduce the gene expression of IL-1β, which seems to play an important role in the pathophysiology of pemphigus
Gustafsson, Gabriel. "Alpha-Synuclein Oligomers : Cellular Mechanisms and Aspects of Antibody Treatment." Doctoral thesis, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-326320.
Повний текст джерелаShih-Jen, Liu, and 劉士任. "Treatment of B-cell Lymphoma with Chimeric Antibody-Cytokine Fusion Proteins." Thesis, 1998. http://ndltd.ncl.edu.tw/handle/20302514994859455580.
Повний текст джерела國防醫學院
生命科學研究所
86
Monoclonal antibodies have been applied to the treatment of cancer in a variety of ways. In this study, we have sought to combine targeting and immuno-potentiation activities by generating a fusion protein that possesses both tumor reactivity and cytokines function. Murine monoclonal antibody S5A8, which recognizes an idiotypic epitope expressed on a murine B cell lymphoma 38C13, was engineered to make anti-Id-cytokine fusion proteins. The heavy- and light-chain variable genes of S5A8 were cloned by PCR and ligated to the corresponding human constant genes in different Ab-expression vectors to produce chimeric S5A8 antibodies (chS5A8) and antibodies with cytokines attached to the carboxyl terminal of the heavy chain to produce chS5A8- IL-2, chS5A8-IL-4, and chS5A8-GM-CSF. The cloned VL and VH genes of S5A8 were ligated with a designed linker with the IL-2 gene conjugated 3'' end to the VH gene to make the single- chain Ab-IL-2 fusion protein (scFvS5A8-IL-2). All engineered proteins retained their specificity to recognize tumor idiotypic antigen, however, the binding affinity varied. The chS5A8, chS5A8- IL-2 , chS5A8-IL-4, and chS5A8-GM-CSF had similar binding affinity as compared with mouse S5A8, but the binding affinity of scFvS5A8-IL-2 was about 12-fold lower than the F(ab) fragment of S5A8. The chS5A8-IL-2, scFvS5A8-IL-2, and chS5A8-GM-CSF maintained full biological activity compared with recombinant IL-2 and GM-CSF, but chS5A8-IL-4 was 5-fold lower than recombinant IL-4. In pharmacokinetics analysis, the cytokine fusion proteins were cleared from the circulation rapidly than the parent antibody S5A8 or chS5A8. In vitro cytotoxicity revealed that chS5A-IL-2 and scFvS5A8-IL-2 could enhance lymphokine-activated-killer (LAK) cell-mediated tumor cell lysis. Furthermore, we showed that chS5A8-IL-2 was proficient in inhibiting tumor growth in vivo more effectively than a combination therapy with anti-Id Abs and IL-2, whereas scFvS5A8-IL-2 did not show any therapeutic effect. These results indicate that the anti-Id-IL-2 fusion protein represents a potent reagent for the treatment for B-cell lymphoma. The effector mechanisms involved in this tumor eradication are not dependent on T cells, since the therapeutic effect of chS5A8-IL2 was not altered in T cell-deficient SCID mice, even in syngeneic mice with depleted CD4+ or CD8+ T cell subsets. In contrast, NK cells are essential for the observed antitumor effect, since therapy with chS5A8-IL-2 is unable to induce tumor eradication in NK- depleted mice or NK function-deficient beige mice. Our data demonstrate that an immunotherapeutic approach using cytokine target by antibodies to tumor sites has a potent effect against B-cell lymphoma.
WANG, XING-MIN, and 王興民. "Treatment of cancer with prodrugs activated by antibody targeted enzyme conjugates." Thesis, 1992. http://ndltd.ncl.edu.tw/handle/30176710188631192529.
Повний текст джерелаYen, Ta-Li, and 閻大立. "Establishment of anti-TMPRSS2 antibody for diagnostic and treatment in prostate cancer." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/ef5wxm.
Повний текст джерела國立臺灣大學
生物化學暨分子生物學研究所
107
Androgen signaling and pericellular proteolysis play important roles in prostate cancer (PCa) progression and metastasis. Among them, type II transmembrane serine proteases II (TMPRSS2) receives an attention because we found that TMPRSS2 could promote PCa cells invasion, tumor growth and metastasis through activation of its proteolytic cascade and extracellular matrix degradation. TMPRSS2 has been also reported to be shed out from cells after its activation. Thus, TMPRSS2 may serve as a biomarker for PCa diagnosis/prognosis and a therapeutic target in PCa. In this thesis, I aimed to generate anti-TMPRSS2 antibodies with a potential of diagnosis, prognosis or therapeutic usages. I used a mammalian secretory expression system to express recombinant TMPRSS2 proteins in CHO cells and purify those proteins from the conditioned media. I successfully used the purified rTMPRSS2 to be antigens for polyclonal antibody generation from a guinea pig and a rabbit. Guinea pig anti-TM2 antibody could recognize the protease domain of TMPRSS2. Rabbit anti-TM2 polyclonal antibody showed a great specificity against TMPRSS2 in cell lysates and could also recognize the shed TMPRSS2 in the conditioned media of PCa cells and PCa patients’ urine samples. The establishment of neutralizing monoclonal antibodies against TMPRSS2 are still undergoing. Thus, the results together indicate that the anti-TM2 antibodies are successfully generated from the animals of guinea pig and rabbit with a potential of clinical application.
Alghuneim, Arwa. "Evaluating the regulation of signaling pathways downstream of CD44 antibody treatment in AML." Thesis, 2019. http://hdl.handle.net/10754/656305.
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