Academic literature on the topic 'Targeted antigen delivery'

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Journal articles on the topic "Targeted antigen delivery"

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Wengerter, Brian C., Joseph A. Katakowski, Jacob M. Rosenberg, Chae Gyu Park, Steven C. Almo, Deborah Palliser, and Matthew Levy. "Aptamer-targeted Antigen Delivery." Molecular Therapy 22, no. 7 (July 2014): 1375–87. http://dx.doi.org/10.1038/mt.2014.51.

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Bourque, Jessica, and Daniel Hawiger. "Applications of Antibody-Based Antigen Delivery Targeted to Dendritic Cells In Vivo." Antibodies 11, no. 1 (January 25, 2022): 8. http://dx.doi.org/10.3390/antib11010008.

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Recombinant immunoglobulins, derived from monoclonal antibodies recognizing the defined surface epitopes expressed on dendritic cells, have been employed for the past two decades to deliver antigens to dendritic cells in vivo, serving as critical tools for the investigation of the corresponding T cell responses. These approaches originated with the development of the recombinant chimeric antibody against a multilectin receptor, DEC-205, which is present on subsets of murine and human conventional dendritic cells. Following the widespread application of antigen targeting through DEC-205, similar approaches then utilized other epitopes as entry points for antigens delivered by specific antibodies to multiple types of dendritic cells. Overall, these antigen-delivery methodologies helped to reveal the mechanisms underlying tolerogenic and immunogenic T cell responses orchestrated by dendritic cells. Here, we discuss the relevant experimental strategies as well as their future perspectives, including their translational relevance.
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Kawasaki, Norihito, Weihsu Chen, Jose Vela, Corwin Nycholat, Igor Maricic, Kumar Vipin, Paul Crocker, Mitchell Kronenberg, and James Paulson. "Efficient lipid antigen presentation to NKT cells by targeting CD169/Siglec-1 on macrophages with its glycan ligand. (100.49)." Journal of Immunology 186, no. 1_Supplement (April 1, 2011): 100.49. http://dx.doi.org/10.4049/jimmunol.186.supp.100.49.

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Abstract Natural killer T (NKT) cells are a subset of T cells expressing an invariant TCR with cross-species conserved specificity to glycolipid antigens in the CD1d restricted presentation. Recent studies have identified CD169/Siglec-1+ macrophages as antigen presenting cells for NKT cells. Here we show that delivery of the lipid antigen through CD169 on macrophages induces NKT cell activation. We developed CD169-targeted liposomes decorated with a specific glycan ligand of CD169 (9-N-biphenylcarboxyl-NeuAcα2-3Galβ1-4GlcNAc) and observed that CD169-targeted liposomes were captured by macrophages in the CD169-dependent manner, and delivered to lysosomes, the known site of lipid antigen loading on CD1d. We next investigated the ability of the CD169-targeted liposomes to promote NKT cell activation by delivery of a lipid antigen α-GalCer to macrophages. We found that macrophages pulsed with α-GalCer containing CD169-targeted liposomes efficiently presented the lipid antigen to NKT cells when transferred into the C57BL/6J mouse. Alternatively, intravenous injection of the α-GalCer containing CD169-targeted liposomes activated NKT cells 100-fold more efficiently than lipid antigen alone in vivo. CD169-targeted liposomes without α-GalCer did not activate NKT cells, demonstrating this activation is through cognate antigen recognition by NKT cells. These data demonstrate that CD169-targeted liposomes dramatically enhance lipid antigen delivery to macrophages for NKT cell activation in vivo.
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Wi, Tae In, Yeongseon Byeon, Ji Eun Won, Jae Myeong Lee, Tae Heung Kang, Jeong-Won Lee, Young Joo Lee, Anil K. Sood, Hee Dong Han, and Yeong-Min Park. "Selective Tumor-Specific Antigen Delivery to Dendritic Cells Using Mannose-Labeled Poly(d, l-lactide-co-glycolide) Nanoparticles for Cancer Immunotherapy." Journal of Biomedical Nanotechnology 16, no. 2 (February 1, 2020): 201–11. http://dx.doi.org/10.1166/jbn.2020.2883.

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A key issue in dendritic cell (DC)-based cancer immunotherapy is the effective delivery of tumor-specific antigens to DCs. To deliver antigens, non-viral vaccine system has been used in ex vivo manipulation. However, ex vivo manipulation is time-consuming, lacks quality control of DCs, and demonstrates low antigen delivery efficiency, which implicates that there are serious problems in therapeutic DC preparations. Therefore, we developed mannose (MN)-labeled poly(d, l-lactide-co-glycolide) (PLGA) nanoparticles (MN-PLGA-NPs) encapsulating tumor-specific antigens for targeted delivery to mannose receptors (MN-R) on DC surfaces without ex vivo manipulation. The MN-PLGA-NPs showed DC-selective delivery in tumor-bearing mice, leading to highly mature and activated DCs, which migrated to lymphoid organs, resulting in activation of cytotoxic CD8+ T cells. Additionally, MN-PLGA-NPs showed significant therapeutic efficacy in EG7 lymphoma tumorbearing mice. Our nano-platform technology can be used as a vaccine system to bypass ex vivo manipulation and enhance targeted delivery of tumor-specific antigens to DCs, which is well-suited for cancer immunotherapy.
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Swanson, Anna, Danli Wu, Isere Kuiatse, Hong-Sung Kim, Helen Heslop, Malcolm Brenner, and Patricia Yotnda. "Delivery of tumor-targeted immunotoxin by tumor-specific T cells (155.19)." Journal of Immunology 186, no. 1_Supplement (April 1, 2011): 155.19. http://dx.doi.org/10.4049/jimmunol.186.supp.155.19.

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Abstract Immunotherapy of cancer using monoclonal antibodies and adoptive transfer of lymphocytes is showing considerable promise. Based on experience with other cancer therapeutics immunotherapeutic modalities, targeting discrete molecular components of the tumor, will prove superior to a single effector system. “Multitargeting” approaches will not only prevent tumor immune escape, they will also allow safer and potent anticancer therapies. We have engineered antigen specific T cells so that they can target tumor cells directly, and then release a potent toxin linked to a monoclonal antibody molecule thereby targeting an independent tumor antigen to the tumor reactive T cell. These engineered T cells were tested in vitro and in vivo in a xenograft model of B-lymphoma. We found that tumor antigen specific T cells retain their anti-tumor activity and tumor homing abilities even when transduced with a gene encoding a chimeric monoclonal antibody-toxin. The release of the targeted immunotoxin molecule occurs only after the T cell has engaged its tumor target. The combination of these two distinct effector systems (T cells and immunotoxin) targeting two distinct tumor antigens have superior anti-tumor activity than a single system targeting a single antigen, with no greater toxicity. By combining two highly specific and partially effective strategies for tumor destruction, we achieved selective and more effective tumor killing.
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Yuba, Eiji, Yoshiki Fukaya, Shin Yanagihara, Nozomi Kasho, and Atsushi Harada. "Development of Mannose-Modified Carboxylated Curdlan-Coated Liposomes for Antigen Presenting Cell Targeted Antigen Delivery." Pharmaceutics 12, no. 8 (August 11, 2020): 754. http://dx.doi.org/10.3390/pharmaceutics12080754.

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Specific delivery to antigen presenting cells (APC) and precise control of the intracellular fate of antigens are crucial to induce cellular immunity that directly and specifically attacks cancer cells. We previously achieved cytoplasmic delivery of antigen and activation of APC using carboxylated curdlan-modified liposomes, which led to the induction of cellular immunity in vivo. APCs express mannose receptors on their surface to recognize pathogen specifically and promote cross-presentation of antigen. In this study, mannose-residue was additionally introduced to carboxylated curdlan as a targeting moiety to APC for further improvement of polysaccharide-based antigen carriers. Mannose-modified curdlan derivatives were synthesized by the condensation between amino group-introduced mannose and carboxy group in pH-sensitive curdlan. Mannose residue-introduced carboxylated curdlan-modified liposomes showed higher pH-sensitivity than that of liposomes modified with conventional carboxylated curdlan. The introduction of mannose-residue to the liposomes induced aggregation in the presence of Concanavalin A, indicating that mannose residues were presented onto liposome surface. Mannose residue-introduced carboxylated curdlan-modified liposomes exhibited high and selective cellular association to APC. Furthermore, mannose residue-introduced carboxylated curdlan-modified liposomes promoted cross-presentation of antigen and induced strong antitumor effects on tumor-bearing mice. Therefore, these liposomes are promising as APC-specific antigen delivery systems for the induction of antigen-specific cellular immunity.
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Murty, Rohan, Abishek Sankaranarayanan, Isabella I. Bowland, Juan Mena-Lapaix, and Mark R. Prausnitz. "Angled Insertion of Microneedles for Targeted Antigen Delivery to the Epidermis." Pharmaceutics 14, no. 2 (February 1, 2022): 347. http://dx.doi.org/10.3390/pharmaceutics14020347.

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Peanut and tree nut allergies account for most food-induced anaphylactic events. The standard allergy immunotherapy approach involves subcutaneous injection, which is challenging because severe adverse reactions can occur when antigens spread systemically. Allergen localization within the epidermis (i.e., the upper 20–100 µm of skin) should significantly reduce systemic uptake, because the epidermis is avascular. Microneedle (MN) patches provide a convenient method for drug delivery to the skin, but they generally target both epidermis and dermis, leading to systemic delivery. In this study, we adapted MN technology for epidermal localization by performing angled insertion of 250 µm–long MNs that limits MN insertion depth mostly to the epidermis. We designed a biplanar insertion device to aid the repeatability of angled insertions into porcine skin ex vivo at specified angles (90°, 45°, and 20°). When compared to 90° insertions, MN application at 20° decreased mean insertion depth from 265 ± 45 µm to 97 ± 15 µm. Image analysis of histological skin sections revealed that acute-angle insertion increased epidermal localization of delivery for antigen-coated MNs from 25% ± 13% to 70% ± 21%. We conclude that angled insertion of MNs can target antigen delivery to epidermis.
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Shaw, Christine A., and Michael N. Starnbach. "Stimulation of CD8+ T Cells following Diphtheria Toxin-Mediated Antigen Delivery into Dendritic Cells." Infection and Immunity 74, no. 2 (February 2006): 1001–8. http://dx.doi.org/10.1128/iai.74.2.1001-1008.2006.

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ABSTRACT Recognition and clearance of many intracellular pathogens requires the activation and subsequent effector functions of CD8+ T lymphocytes. To stimulate CD8+ T cells by immunization, the target antigens must be delivered into the cytosol of host cells. There they can be processed into peptides and presented in the context of major histocompatibility complex class I molecules to antigen-specific CD8+ T cells. One method of delivering antigens into the cytosol is to fuse them to modified bacterial toxins that are able to enter mammalian cells. The expression pattern of the toxin receptors in the host will determine the cell population that the toxin fusion protein targets and will thus restrict antigen-specific T-cell recognition to the same population. In this study we describe the development and characterization of a diphtheria toxin (DT)-based antigen delivery system. Using CD11c-DTR transgenic mice that express the DT receptor in dendritic cells (DC), this system allows for targeted delivery of CD8+ T-cell antigen to DC. We show that antigen-specific CD8+ T cells proliferate in CD11c-DTR mice following immunization with catalytically inactive DT-antigen fusion proteins. We also show that a toxin-based system that restricts antigen delivery to DC results in more robust antigen-specific CD8+ T-cell proliferation than a toxin-based system that does not restrict delivery to a particular cell type. These results have implications for vaccine design, and they suggest that use of a toxin-based vector to target antigen to DC may be an effective way to induce a CD8+ T-cell response.
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Ciccotelli, Jo Erika, Helene Toussaint, Geza Erdos, Cara Carey, Simon Watkins, and Louis Falo. "Intradermal immunization with polyguanine conjugated antigens enables targeted and sustained delivery of protein antigens to dendritic cells in vivo. (APP3P.111)." Journal of Immunology 192, no. 1_Supplement (May 1, 2014): 111.12. http://dx.doi.org/10.4049/jimmunol.192.supp.111.12.

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Abstract Effective vaccine design depends on the ability to target specific antigens to antigen presenting cells (APCs), including dendritic cells (DCs). Conjugation of proteins antigens to polyguanine (Poly(dG)) molecules is a novel immunization approach capable of transforming soluble antigens into aggregated particulates with exposed scavenger receptor (SR) ligands. We have previously shown that Poly(dG) conjugation to protein antigen results in increased antigen-specific helper and cytotoxic T cell responses, memory T cell induction, and antibody titers. Here, we specifically investigate mechanisms of Poly(dG)-conjugated antigen delivery and internalization. Compared to soluble OVA, Poly(dG)-OVA is rapidly and more efficiently internalized by bone marrow derived DCs in vitro, and this internalization is inhibited by scavenger receptor blockade. Importantly, in a mouse model intradermally injected Poly(dG)-OVA results in antigen persistence in the skin for up to 7 days. This is accompanied by increased antigen uptake by skin resident DCs and persistent migration of antigen loaded DCs to the draining lymph nodes. DCs exposed to Poly(dG)-OVA had increased expression of CCR7 and secretion of MCP-1, TNF-α, and IL-6. These results suggest that coupling Poly(dG) to protein antigens enables efficient DC targeting through SRs, prolonged delivery of antigens in vivo, and activation of innate immunity. This approach may be used to design more efficient antiviral and antitumor vaccines.
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Raiber, Eun-Ang, Calogero Tulone, Yanjing Zhang, Luisa Martinez-Pomares, Emily Steed, Anna M. Sponaas, Jean Langhorne, Mahdad Noursadeghi, Benjamin M. Chain, and Alethea B. Tabor. "Targeted Delivery of Antigen Processing Inhibitors to Antigen Presenting Cells via Mannose Receptors." ACS Chemical Biology 5, no. 5 (April 27, 2010): 461–76. http://dx.doi.org/10.1021/cb100008p.

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Dissertations / Theses on the topic "Targeted antigen delivery"

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Rohrbach, Florian. "Induction of anti-tumor immunity by targeted delivery of ErbB2 cancer vaccines to antigen-presenting cells." Université Louis Pasteur (Strasbourg) (1971-2008), 2004. http://www.theses.fr/2004STR13026.

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Stylianou, Elena. "Specific cell-targeted delivery of mycobacterial antigens in vivo." Thesis, St George's, University of London, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.546779.

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Schumacher, Dominik. "Site-specific functionalization of antigen binding proteins for cellular delivery, imaging and target modulation." Doctoral thesis, Humboldt-Universität zu Berlin, 2017. http://dx.doi.org/10.18452/18547.

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Antikörper und Antigen-bindende Proteine, die an Fluorophore, Tracer und Wirkstoffe konjugiert sind, sind einzigartige Moleküle, welche die Entwicklung wertvoller diagnostischer und therapeutischer Werkzeuge ermöglichen. Allerdings ist der Konjugationsschritt sehr anspruchsvoll und trotz intensiver Forschung noch immer ein bedeutender Engpass. Zusätzlich sind Antigen-bindende Proteine oftmals nicht dazu in der Lage, die Zellmembran zu durchdringen und im Zellinneren nicht funktionsfähig. Daher ist ihre Verwendung auf extrazelluläre Targets beschränkt, was eine bedeutende Anzahl wichtiger Antigene vernachlässigt. Beide Limitierungen bilden Kernaspekte dieser Arbeit. Mit Tub-tag labeling wurde ein neuartiges und vielseitiges Verfahren für die ortsspezifische Funktionalisierung von Biomolekülen und Antigen-bindenden Proteinen entwickelt, und so die Palette der Proteinfunktionalisierungen bedeutend erweitert. Tub-tag wurde erfolgreich für die ortsspezifische Funktionalisierung verschiedener Proteine und Antigen-bindender Nanobodies angewendet, die für konfokale Mikroskopie, Proteinanreicherung und hochauflösende Mikroskopie eingesetzt wurden. In einem weiteren Projekt wurden zellpermeable Antigen-bindende Nanobodies hergestellt und somit das schon lange Zeit bestehende Ziel, intrazelluläre Targets durch in vitro funktionalisierte Antigen-bindende Proteine zu visualisieren und manipulieren, erreicht. Hierzu wurden zwei verschiedene Nanobodies an ihrem C-Terminus cyclischen zellpenetrierenden Peptiden unter Verwendung von Expressed Protein Ligation funktionalisiert. Diese Peptide ermöglichten die Endozytose-unabhängige Aufnahme der Nanobodies mit sofortiger Bioverfügbarkeit. Mit Tub-tag labeling und der Synthese von zellpermeablen Nanobodies konnten wichtige Bottlenecks im Bereich der Proteinfunktionalisierung und Antikörperforschung adressiert werden und neue Tools für die biochemische und zellbiologische Forschung entwickelt werden.
Antibodies and antigen binding proteins conjugated to fluorophores, tracers and drugs are powerful molecules that enabled the development of valuable diagnostic and therapeutic tools. However, the conjugation itself is highly challenging and despite intense research efforts remains a severe bottleneck. In addition to that, antibodies and antigen binding proteins are often not functional within cellular environments and unable to penetrate the cellular membrane. Therefore, their use is limited to extracellular targets leaving out a vast number of important antigens. Both limitations are core aspects of the presented thesis. With Tub-tag labeling, a novel and versatile method for the site-specific functionalization of biomolecules and antigen binding proteins was developed expanding the toolbox of protein functionalization. The method is based on the microtubule enzyme tubulin tyrosine ligase. Tub-tag labeling was successfully applied for the site-specific functionalization of different proteins including antigen binding nanobodies which enabled confocal microscopy, protein enrichment and super-resolution microscopy. In addition to that, cell permeable antigen binding nanobodies have been generated constituting a long thought goal of tracking and manipulating intracellular targets by in vitro functionalized antigen binding proteins. To achieve this goal, two different nanobodies were functionalized at their C-terminus with linear and cyclic cell-penetrating peptides using expressed protein ligation. These peptides triggered the endocytosis independent uptake of the nanobodies with immediate bioavailability. Taken together, Tub-tag labeling and the generation of cell-permeable antigen binding nanobodies strongly add to the functionalization of antibodies and their use in biochemistry, cell biology and beyond.
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Polak, Roberta. "Desenvolvimento e fabricação de filmes ultra-­finos, obtidos pela técnica layer-by-layer, para aplicações na entrega direcionada de fármacos e na captura seletiva de bio-­marcadores." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/9/9135/tde-27042015-152718/.

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O objetivo geral deste trabalho foi explorar a versatilidade de filmes multicamadas de polieletrólitos (PEM) e suas aplicações em sistemas de entrega de drogas e como filmes funcionais para aplicações biomédicas. Filmes PEM montados pela técnica de camada por camada (layer­-by­-layer, LbL), foram explorados em três aplicações principais. Na primeira, foi explorado o desenvolvimento de um protocolo de funcionalização em filmes de poli(alilamina)/poli (estireno sulfonato), PAH/SPS. Os parâmetros de construção do filme para biotinilação dos grupamentos amina do PAH foram otimizados e aplicados na captura e detecção do antígeno específico da próstata (PSA), na concentração de 100 a 0,1 ng/mL, usando pontos quânticos (Qdots). Em comparação com outros trabalhos, este sistema apresentou uma boa sensibilidade na detecção de PSA, dentro do limite de detecção clínica de 0,4 a 0,1 ng/mL. A segunda aplicação envolveu o desenvolvimento de filmes de sacrifício baseados nas interações naturais da mucina submandibular bovina e da lectina, jacalina (BSM/JAC). Filmes de BSM/JAC apresentaram estabilidade quando submetidos a uma ampla faixa de pH (pH 3-­-9) e em solução de alta força iônica (5 M NaCl). A dissolução dos filmes BSM/JAC pôde ser seletivamente desencadeada mediante à incubação em solução de melibiose, 37 °C, pH 7,4, sem apresentar citotoxicidade às células. Na última parte deste trabalho, a incorporação de lipossomos ecogênicos (ELIP) em mochilas celulares foi investigada. Mochilas celulares são \"patches\" de 7­-10 µm de diâmetro que podem ser fabricados por meio de deposição alternada de polímeros utilizando-­-se a técnica de LbL, sobre uma matriz pré­-moldada obtida por fotolitografia, a fim de criar um sistema composto por três multicamadas estratificadas: uma região de liberação, para promover o destacamento do substrato, uma região de carga de droga, e uma região adesiva às células. O uso de ELIP permitiu incorporação de até 9x mais doxorrubicina (DOX) se comparado com o fármaco livre em solução absorvido pelos dos filmes. A liberação de DOX pelos filmes foi monitorado por 25 dias. Mochilas contendo ELIP-­DOX foram então aderidos a monócitos, e sua viabilidade monitorados por 72h. Mochilas vazias mostraram diminuir a proliferação de monócitos ao longo das 72 horas, enquanto mochilas carregadas com ELIP-­DOX mostraram uma diminuição dramática na população celular, apontando uma potencialização dos efeitos da droga pela sua proximidade com as células.
The overall goal of this thesis was to exploit the versatility of polyelectrolite multilayers (PEM) to be applied in drug delivery systems and biofunctionalizable films for biomedical applications. PEM films assembled by the layer-by­-layer technique were explored in three main applications. In the first part of this work, the development of a functionalization protocol of poly(allylamine)/poly(styrene sulfonate), PAH/SPS was explored. The optimal film parameters to the use of biotinylated multilayers were applied for the capture and detection of prostate specific antigen (PSA) protein in the range of 100 to 0.1 ng/mL, by using quantum dots. Compared to previous work, this system presented a good sensitivity for PSA detection that is within the clinical limit range of 0.4 to 0.1 ng/mL. The second application involved the creation of a novel sacrificial multilayer film. Films based in natural interactions of bovine submaxillary mucin and the lectin jacalin, BSM/JAC were assembled. BSM/JAC films showed stability when underwent a wide rage of pH (pH 3 to 9) and high ionic strength (5 M NaCl) solutions. BSM/JAC dissolution could be triggered released by incubation in melibiose at 37 °C in pH 7.4 buffer, without cytotoxicity. In the last part of this work the incorporation of echogenic liposomes (ELIP) into cell backpacks was investigated. Cell backpacks are 7-10 µm diameter patches that can be fabricated through LbL polymer deposition onto a photopatterned array to create a stacked composite of three stratified multilayer systems: a releasable region for easy detachment from the substrate, a drug payload region, and a cell adhesive region. The use of ELIP allowed up to 9x more doxorubicin (DOX) loading when compared to free drug in solution adsorbed through the films. DOX release from films was monitored for over 25 days. ELIP­-DOX backpacks were then attached to mouse monocytes and their viability monitored by 72h. Empty backpacks showed to decrease monocytes proliferation over the course of 72h, while ELIP­-DOX backpacks showed a dramatic decrease in cell population, showing that DOX effects were enhancement in drug potency by its proximity.
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Chu, Hin Lun. "Intracellular delivery of radioimmunoconjugates that target the cancer testis antigen, NY-ESO-1." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:84c830c4-c216-4b2c-8383-e1119d77c295.

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Cancer testis antigens (CTA) represent attractive targets for targeted radiotherapy and imaging as their expression is restricted to cancer and germ cells. NY-ESO-1, a member of the CTA family, is highly immunogenic and expressed in multiple tumor types including carcinoma of bladder, liver lung. The aim of this study was to develop radioimmunoconjugates (RIC) to target NY-ESO-1 protein in cancer cells. Anti-NY-ESO-1 antibodies were modified by addition of DTPA for 111In-labelling or, in the presence of Iodogen, were 123I-labelled. Delivery of radiolabeled immunoconjugates across the cell membrane was achieved using a protein transfection (PT) reagent (SAINT-PhD) and by chemical linkage with the cell-penetrating and nuclear-localizing peptide, TAT (YGRKKRRQRRR). Cellular internalization, distribution and efflux of 111In-DTPA-anti-NY-ESO-1-TAT-PT and 123I-anti-NY-ESO-1-TAT-PT were investigated in cell fractionation and retention assays. It was shown that protein transfection reagent has promoted the cellular uptake of RICs into SK-MEL-37 and both of 111In-DTPA-anti-NY-ESO-1-TAT-PT and 123I-anti-NY-ESO-1-TAT-PT was retained longer in SK-MEL-37 cells in comparison to their isotope control RIC. In clonogenic assays, 111In-DTPA-anti-NY-ESO-1-TAT-PT significantly reduced surviving fraction of SK-MEL-37 cells. Cytotoxicity was inversely proportional to specific activity and the concentration of cells exposed to 111In-DTPA-anti-NY-ESO-1-TAT-PT. siRNA knock down of NY-ESO-1 resulted in partial reversal of 111In-DTPA-anti-NY-ESO-1-TAT-PT associated cytotoxicity. These promising results obtained from the in vitro study has brought the probe further into in vivo study. In preliminary biodistribution studies in SK-MEL-37 xenograft-bearing mice, tumour:muscle ratio for 111In-DTPA-anti-NY-ESO-1-TAT-PT was statistically significant compared to the control RIC 48 h post injection. This clearly indicated that the probe can be delivered into tumour in in vivo model and the successful uptake of radioactivity increased the chance of causing cytotoxicity to tumour cells through DNA damage. All of these findings have suggested that intracellular cancer associated antigen NY-ESO-1 can be reached by protein transfection reagent and cell penetrating peptide and initiates DNA damage through radio-isotope mediated cytotoxicity. Therefore, it represents a novel approach to the treatment of CTA-expressing cancers.
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Schumacher, Dominik [Verfasser], Christian P. R. [Gutachter] Hackenberger, Dorothea [Gutachter] Fiedler, and Heinreich [Gutachter] Leonhardt. "Site-specific functionalization of antigen binding proteins for cellular delivery, imaging and target modulation / Dominik Schumacher ; Gutachter: Christian P. R. Hackenberger, Dorothea Fiedler, Heinreich Leonhardt." Berlin : Humboldt-Universität zu Berlin, 2017. http://d-nb.info/1185578390/34.

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Pereira, Inês Sousa. "Carcinoembryonic antigen targeted polymeric nanoparticles for drug delivery." Master's thesis, 2017. https://hdl.handle.net/10216/108253.

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Pereira, Inês Sousa. "Carcinoembryonic antigen targeted polymeric nanoparticles for drug delivery." Dissertação, 2017. https://hdl.handle.net/10216/108253.

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Whipple, Emily Christine. "Targeted delivery of antigens to follicular dendritic cells via a monoclonal antibody specific for complement receptor 2 on marginal zone B cells : dynamics of delivery and applications towards vaccine development /." 2006. http://wwwlib.umi.com/dissertations/fullcit/3235122.

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Blažková, Kristýna. "Chemicky modifikované částice z myšího polyomaviru a jejich interakce s membránově vázaným nádorovým antigenem specifickým pro prostatu (PSMA)." Master's thesis, 2014. http://www.nusl.cz/ntk/nusl-337154.

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Prostate cancer is one of the most abundant types of cancer among men and the demand for a specific treatment is very high. In this thesis, I have focused on using Glutamate Carboxypepti- dase II (GCPII), as a target for a proof-of-principle delivery system. GCPII is a transmembrane protein that internalizes after a binding of a ligand and is overexpressed in prostate cancer. Virus-like particles from Murine polyomavirus (VLPs) are a suitable nanocarrier for the delivery of imaging agents and drugs. Here I describe modifying these VLPs with inhibitors of GCPII and fluorescent dyes and characterize their binding to GCPII on surface plasmon resonance and to cells expressing GCPII on confocal microscopy. VLPs carrying a GCPII inhibitor show specific binding to GCPII on surface plasmon reso- nance, however they bind non-specifically to cells that don't express GCPII. Several approaches have been tried to avoid that. The substitution of BC loop on the exterior surface of VLPs that is partially responsible for the binding of sialic acid did not seem to affect specificity on cells. Another approach tested was coating of the wild-type VLPs with large polymer carrying a flu- orescent label and a GCPII inhibitor. After the conjugation of the polymer to the VLP, specific binding and internalization in GCPII-positive...
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Books on the topic "Targeted antigen delivery"

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Manoury, Bénédicte, and Piergiuseppe De Berardinis, eds. Targeted Antigen Delivery: Bridging Innate and Adaptive Immunity. Frontiers Media SA, 2019. http://dx.doi.org/10.3389/978-2-88945-833-2.

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Gordon, Siamon. Macrophage As Therapeutic Target. Springer London, Limited, 2012.

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Gordon, Siamon. The Macrophage as Therapeutic Target. Springer, 2012.

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The Macrophage as Therapeutic Target. Springer, 2003.

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Book chapters on the topic "Targeted antigen delivery"

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Dobrica, Mihaela-Olivia, Catalin Lazar, and Norica Branza-Nichita. "Production of Chimeric Hepatitis B Virus Surface Antigens in Mammalian Cells." In Vaccine Delivery Technology, 83–94. New York, NY: Springer US, 2020. http://dx.doi.org/10.1007/978-1-0716-0795-4_7.

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Abstract The small (S) envelope protein of the Hepatitis B Virus (HBV), HBV-S, has the unique ability to self-assemble into highly immunogenic subviral particles (SVPs), in the absence of other viral factors, in eukaryotic cells, including those of nonhepatic origin. This feature is currently exploited for generation of SVPs exposing heterologous epitopes on their surface that can be used as vaccine candidates to target various diseases. Here, we describe a simple and robust method for production of such chimeric HBV-S protein-based SVPs in transiently transfected HEK293T cells and purification from cell supernatants by ultracentrifugation on sucrose cushion and sucrose step gradients. The SVPs obtained by this methodology have been successfully used in immunogenicity studies in animal models.
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Palacio-Castañeda, Valentina, Roland Brock, and Wouter P. R. Verdurmen. "Generation of Protein-Phosphorodiamidate Morpholino Oligomer Conjugates for Efficient Cellular Delivery via Anthrax Protective Antigen." In Methods in Molecular Biology, 129–41. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2010-6_8.

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AbstractPhosphorodiamidate morpholino oligomers (PMOs) offer great promise as therapeutic agents for translation blocking or splice modulation due to their high stability and affinity for target sequences. However, in spite of their neutral charge as compared to natural oligonucleotides or phosphorothioate analogs, they still show little permeability for cellular membranes, highlighting the need for effective cytosolic delivery strategies. In addition, the implementation of strategies for efficient cellular targeting is highly desirable to minimize side effects and maximize the drug dose at its site of action. Anthrax toxin is a three-protein toxin of which the pore-forming protein anthrax protective antigen (PA) can be redirected to a receptor of choice and lethal factor (LF), one of the two substrate proteins, can be coupled to various cargoes for efficient cytosolic cargo delivery. In this protocol, we describe the steps to produce the proteins and protein conjugates required for cytosolic delivery of PMOs through the cation-selective pore generated by anthrax protective antigen. The method relies on the introduction of a unique cysteine at the C-terminal end of a truncated LF (aa 1–254), high-yield expression of the (truncated) toxin proteins in E. coli, functionalization of a PMO with a maleimide group and coupling of the maleimide-functionalized PMO to the unique cysteine on LF by maleimide-thiol conjugation chemistry. Through co-administration of PA with LF-PMO conjugates, an efficient cytosolic delivery of PMOs can be obtained.
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Kandil, Rima, Daniel Feldmann, Yuran Xie, and Olivia M. Merkel. "Evaluating the Regulation of Cytokine Levels After siRNA Treatment in Antigen-Specific Target Cell Populations via Intracellular Staining." In Nanotechnology for Nucleic Acid Delivery, 323–31. New York, NY: Springer New York, 2019. http://dx.doi.org/10.1007/978-1-4939-9092-4_21.

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Pradeep, Andrew, R. Sethu Nagarajan, and H. Fazil. "Immune-Targeted Nanomedicine." In Handbook of Research on Nano-Strategies for Combatting Antimicrobial Resistance and Cancer, 294–305. IGI Global, 2021. http://dx.doi.org/10.4018/978-1-7998-5049-6.ch014.

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Immunotherapy has become a preferable candidate for many diseases in recent days. The infusion or administration of immune complexes or components to elicit the own immune response against a particular disease by attracting the antigen presenting cells against the disease causing organism and eliciting the T-cell mediated killing and further activating cell mediated immunity based on the processed surface antigens underlies the basic concept behind the immunotherapy. Immunotherapy can be applied for all course of diseases even in the treatment of cancer. The limitation in using immunotherapy is that it needs a proper delivery vehicle to reach the diseased spot to shows its pharmacokinetic property. In case of cancer, the immune components administered itself are not able to pertain and penetrate the solid tumor mass. Nanoparticles are small-sized particles which are generally specific in action used in the field of medicine. Nanoparticles aid in targeted drug delivery to the specific spots and immune targeting of nanoparticles is due to its enhanced permeability and retention (EPR).
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Bhattacharya, Sankha, and Kapil Gore. "Targeted Cancer Therapy Using Nanoparticles and Antibody Fragments." In Advances in Precision Medicine Oncology. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.96550.

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Cancer is caused by an uncontrolled cell division, forming a tumor capable of metastasis. Cancer is the second leading cause of death worldwide. Conventional treatments kill healthy cells, causing side effects. Recently, nanomaterials are explored due to properties such as as- nano-size, high loading, and ligands’ attachment for a selective delivery. Apart from normal body cells, cancer cells express many receptors in excess, which serve as ‘targets’ for attacking the cells. Various ligands like proteins, peptides, polysaccharides can be attached to nanoparticles to allow proper and specific reach to the tumor. Such nanoparticles go to their desired site and stick onto the receptors, taken inside the cells by various methods. Antibodies are natural proteins that bind to foreign substances and remove them. IgG being the most explored antibody, suffers from many disadvantages such as non-specificity for required antigen, limited binding sites, low tumor penetration. Hence many researchers experimented by removing and adjusting the binding sites, using only the binding sites, enhancing the valency of naturally available IgG. It gave many benefits such as enhanced penetration, reduced immunogenicity, better delivery of drugs with fewer side effects. Continuing advancements in the field of protein engineering will help scientists to come up with better solutions. The properties allow easy surface interaction and entry, achieve better biodistribution, and reduce the amount of drug required. Targeting is based on Paul Ehrlich’s ‘magic bullet, ‘where the therapeutic moiety has two parts-one to identify the target and the second to eliminate it. This concept is revised to incorporate a third component, a carrier. Many nanocarriers can be used to target cancer cells containing ligands to identify malignant cells. Approaches to targeting are passive, active and physical targeting. Many such nanoparticles are in clinical trials and can be a better solution to cancer therapy.
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Singh, M. "Use of Nanomaterials-based Enzymes in Vaccine Production and Immunization." In Nanomaterial-Supported Enzymes, 240–60. Materials Research Forum LLC, 2022. http://dx.doi.org/10.21741/9781644901977-9.

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The production of standard vaccines is increasing rapidly. The improvement is needed due to соnсerns of low immunogenicity, instability, and the need for more vассines. To оverсоme these concerns, development of vассines has been integrated with and facilitated by nanotechnology. Nanotechnology is increasingly рlаying а key role in vaccination by the development of NP-based delivery systems which have aided in increasing cellular and humoral immune responses. The nano carrier-based system facilitates the delivery of vaccine antigens to target cells and increases antigen resistance and immunogenicity. Many nano-sized particles have been studied and are being used as adjuvants and vehicles to deliver vaccine antigens. The efficiency of NPs as nanocarriers is due to their size and рrоmоting specialized and selective immune responses. This сhарter will focus on nanonzyme аnd their use in vассine prоduсtiоn аnd immunizаtiоn.
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Peine, Kevin J., Naihan Chen, Eric M. Bachelder, and Kristy M. Ainslie. "Drug Delivery Strategies for Tolerogenic Therapy for Autoimmune Diseases in an Antigen-Specific Manner." In Chronic Illness and Long-Term Care, 112–40. IGI Global, 2019. http://dx.doi.org/10.4018/978-1-5225-7122-3.ch007.

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Autoimmune diseases are the result of an improper immune response towards a self-antigen. Predominantly, autoimmune diseases have been treated using therapies that suppress systemic immune responses, which can result in significant side-effects like increased risk of infection and cancer. Alternatively, induction of immune tolerance through antigen-specific therapies can inhibit disease-associated responses without systemic suppression. Previously, immune tolerance has been accomplished by soluble antigen delivery through oral, nasal or sublingual routes. However, these therapies have shown minimal success in clinical settings. In an attempt to increase the efficacy of these therapies, recent work has utilized microparticulate delivery vehicles for the induction of immune tolerance. Microparticles are capable of increasing the solubility and circulation of cargo. In addition, their ability to passively target macrophages and dendritic cells increases their capacity for modulating the immune response. Recent work has shown microparticles fabricated with disease-associated antigens have limited disease progression and severity in animal models of Multiple Sclerosis, Type 1 Diabetes and Rheumatoid Arthritis. Inhibition of disease progression has corresponded with an antigen-specific decrease in inflammatory responses. The emerging field of inducing tolerance through microparticle-based therapies can limit therapeutic side-effects and increase patient quality of life by providing for long-term suppression of autoimmune disorders without compromising systemic immune function.
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Bicak, Bilge, Serda Kecel Gunduz, and Aysen E. Ozel. "Advancements in Cancer Therapeutics." In Handbook of Research on Advancements in Cancer Therapeutics, 382–412. IGI Global, 2021. http://dx.doi.org/10.4018/978-1-7998-6530-8.ch013.

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Targeted drug delivery in cancer treatment is a very convenient method for increasing the effectiveness of drugs and reducing their toxic side effects. Nano drug delivery systems have unique physical, chemical, mechanical, and optical properties. Nanoparticles, which have large surface areas and functional groups for the binding of therapeutic agents, benefit the drug distribution with nanoparticle formulations and can provide new features. They also enable personal oncology for diagnosis and treatment, which is appropriate for the personal molecular profile structures of cancer patients. The tumor-targeted active substances are attached to nanoparticles and the active substance loaded nanoparticles are targeted to the tumor area; these nanoparticles can be used with a high tendency to bind and specificity, to target tumor antigens or vessels. This chapter, besides traditional chemotherapy and radiotherapy methods in the field of cancer treatment, is aimed to give information about targeted drug delivery systems for cancer cell targeting without damaging normal tissues.
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Rajeswari, P. Raja, S. Viswanadha Raju, Amira S. Ashour, and Nilanjan Dey. "Insilico Approach for Epitope Prediction toward Novel Vaccine Delivery System Design." In Advances in Multimedia and Interactive Technologies, 256–66. IGI Global, 2017. http://dx.doi.org/10.4018/978-1-5225-1025-3.ch012.

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Vaccines build a defense mechanism against the disease causing agents through the immune system stimulation and disease agents' imitation. Some of the vaccines contain a part of the disease causing agents that are either weakened or dead. Along with using vaccines with viral infections, it can be used against the various types of cancers for both therapy and prevention. The use of cancer's vaccines in cancer therapies is called immunotherapy. It can be done either by specific cancer vaccine or universal cancer vaccine that contains tumor antigens, which stimulate the immune system. This in turn initiates various mechanisms that terminate tumor cells and prevents recurrence of these tumors. The present work proposed an Insilico approach in epitope prediction and analysis of antigenecity and Immunogenecity of Haemophilus influenzae strains. It was interested with the design of a novel vaccine delivery system with better adjuvancity, where vaccine adjuvant is significant for the improvement of the antigens' immunogenicity that present in the vaccines. The conducted insilico approaches selected the best strain target proteins, m strain selection, epitope prediction, antigenicity and immunogenicity prediction of target proteins to find out the best targets.
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Rachmawati, Hidajah, Raditya Weka Nugraheni, and Firasti A.N. Sumadi. "In-Silico Approach in the Development of Salmonella Epitope Vaccine." In Salmonella - a Challenge From Farm to Fork [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.96313.

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In the case of infection control, one of our primary concerns is typhoid fever. According to WHO, typhoid prevalence in Indonesia is highly endemic. There is also the problem with the low efficacy of the available vaccine to prevent the disease. Therefore, there is an urgent need to develop a highly effective typhoid vaccine. One of the phases in vaccine development is an exploratory phase, a research-intensive phase of the vaccine development process designed to identify natural or synthetic antigens that might help prevent or treat a disease through computer in silico prediction targets. The vaccines developed through epitope peptide are designed to be safer, more efficacious, and less expensive than traditional vaccines. A thorough understanding of the disease agent, particularly critical epitopes to induce the appropriate immunological reaction, is required to achieve these aims. Mapping epitope sequences or antigenic peptides from pathogenic proteins recognized by B cells and T cells is crucial for vaccine development. Once the epitopes were identified, the polypeptide production could be produced through protein recombinant technology. The polypeptide vaccine, in the end, could be delivered using a liposomal delivery system.
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Conference papers on the topic "Targeted antigen delivery"

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Zhang, Lei, Feiyu Lu, Ibrahim Asadullah Tahmid, Shakiba Davari, Lee Lisle, Nicolas Gutkowski, Luke Schlueter, and Doug A. Bowman. "Fantastic Voyage 2021: Using Interactive VR Storytelling to Explain Targeted COVID-19 Vaccine Delivery to Antigen-presenting Cells." In 2021 IEEE Conference on Virtual Reality and 3D User Interfaces Abstracts and Workshops (VRW). IEEE, 2021. http://dx.doi.org/10.1109/vrw52623.2021.00230.

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Banerjee, Rupak K., Meinrad Praxmaraer, Ilhan Dilber, Peter Bungay, William van Osdol, and Cynthia Sung. "Numerical Simulation of Antibody Penetration in a Solid Tumor Nodule Using Finite Element Method." In ASME 1998 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 1998. http://dx.doi.org/10.1115/imece1998-0058.

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Abstract The high binding specificity that monoclonal antibodies exhibit has led to great interest in using them to target tumor-associated antigens. The antibody may be coupled to a radionuclide or cytotoxic drug to create a tumor-targeted reagent that can be used to identify sites of metastatic disease and/or deliver a lethal substance to the tumor cells. However, successful application of these compounds in a clinical setting has been hindered by a poor understanding of the factors that govern antibody accumulation in a tumor. We have used a finite element method to develop a pharmacokinetic model describing the uptake of systemically-administered antibody in an early, prevascular spherical tumor nodule embedded in normal tissue. The model incorporates such processes as plasma kinetics, transcapillary transport, interstitial diffusion, binding reactions, lymphatic clearance, and antigen internalization.
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Cremel, Magali, Nathalie Guerin, Quitterie Barthe, Vanessa Bourgeaux, Willy Berlier, Françoise Horand, and Yann Godfrin. "Abstract 2356: Erythrocytes used as tumor antigen delivery system to target antigen-presenting cells embody an innovative approach forin situcancer immunotherapy." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-2356.

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Cheung, Lawrence H., Khalid A. Mohamedali, Walter N. Hittelman, and Michael G. Rosenblum. "Abstract 2780: Engineering human fusion constructs for targeted delivery of granzyme B to CD33 and CEA antigens." In Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-2780.

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Asundi, Jyoti, Lisa Crocker, Jarrod Tremayne, Paul Polakis, and Ron Firestein. "Abstract 947: An antibody drug conjugate (ADC) directed to lymphocyte antigen 6 complex, locus E (LY6E) delivers targeted chemotherapy to a wide range of solid tumor malignancies." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-947.

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Reports on the topic "Targeted antigen delivery"

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Palmer, Guy, Varda Shkap, Wendy Brown, and Thea Molad. Control of bovine anaplasmosis: cytokine enhancement of vaccine efficacy. United States Department of Agriculture, March 2007. http://dx.doi.org/10.32747/2007.7695879.bard.

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Anaplasmosis an arthropod-born disease of cattle caused by the rickettsia Anaplasma marginale and is an impediment to efficient production of healthy livestock in both Israel and the United States. Currently the only effective vaccines are derived from the blood of infected cattle. The risk of widespread transmission of both known and newly emergent pathogens has prevented licensure of live blood-based vaccines in the U.S. and is a major concern for their continued use in Israel. Consequently development of a safe, effective vaccine is a high priority. In this collaborative project we focused on two approaches to vaccine development. The first focused o n improving antigen delivery to livestock and specifically examined how DNA vaccines could be improved to enhance priming and expansion of the immune response. This research resulted in development and testing of two novel vaccine delivery systems--one that targeted antigen spread among dendritic cells (the key cell in priming immune responses and a follow-on construct that also specifically targeted antigen to the endosomal-lysosomal compartment the processing organelle within the dendritic cell that directs vaccine antigen to the MHC class ll-CD4* T cell priming pathway). The optimized construct targeting vaccine antigen to the dendritic cell MHC class II pathway was tested for ability to prime A. marginale specific immune responses in outbred cattle. The results demonstrated both statistically significant effects of priming with a single immunization, continued expansion of the primary immune response including development of high affinity lgG antibodies and rapid recall of the memory response following antigen challenge. This portion of the study represented a significant advance in vaccine delivery for livestock. Importantly the impact of these studies is not limited to A. marginale a s the targeting motifs are optimized for cattle and can be adapted to other cattle vaccinations by inserting a relevant pathogen-specific antigen. The second approach (which represented an addition to the project for which approval was requested as part of the first annual report) was a comparative approach between A . marginale and the Israel A . centrale vaccines train. This addition was requested as studies on Major Surface Protein( MSP)- 2 have shown that this antigen is highly antigenically variable and presented solely as a "static vaccine" antigen does not give cross-strain immunity. In contrast A. . centrale is an effective vaccine which Kimron Veterinary institute has used in the field in Israel for over 50 years. Taking advantage of this expertise, a broad comparison of wild type A. marginale and vaccine strain was initiated. These studies revealed three primary findings: i) use of the vaccine is associated with superinfection, but absence of clinical disease upon superinfection with A. marginale; ii) the A. centrale vaccine strain is not only less virulent but transmission in competent in Dermacentor spp. ticks; and iii) some but not all MSPs are conserved in basic orthologous structure but there are significant polymorphisms among the strains. These studies clearly indicated that there are statistically significant differences in biology (virulence and transmission) and provide a clear path for mapping of biology with the genomes. Based on these findings, we initiated complete genome sequencing of the Israel vaccine strain (although not currently funded by BARD) and plant to proceed with a comparative genomics approach using already sequenced wild-type A. marginale. These findings and ongoing collaborative research tie together filed vaccine experience with new genomic data, providing a new approach to vaccine development against a complex pathogen.
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