TR&D1: Engineering artificial Antigen Presenting Cells, aAPC, for Adoptive Immunotherapy

基本信息

批准号：
10436870
负责人：
JONATHAN P SCHNECK
金额：
$ 31.76万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-15 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10436870
关键词：
Address Adoption Adoptive Immunotherapy Antibodies Antigen-Presenting Cells Antigenic Specificity Antigens Autoantigens Autoimmune Diseases Autoimmunity Biological Biological Models Biomimetics CD28 gene CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes CD8B1 gene Cell Therapy Cells Cellular immunotherapy Chronic Clinical Complex Coupled Development Disease Effector Cell Engineering Formulation Frequencies Goals HLA-A2 Antigen Human Immunotherapeutic agent Immunotherapy In Vitro Lesion Ligands Magnetism Memory Metabolic Modeling Mus Patients Peptide/MHC Complex Phase I Clinical Trials Phenotype Preparation Process Production Protocols documentation Research Resistance Safety Signal Transduction System T cell therapy T-Lymphocyte Technology Time Translational Research Translations Tumor Antigens Virus Diseases Work antigen-specific T cells base cancer immunotherapy cancer therapy cost density design humanized mouse immunoengineering immunoregulation improved in vivo innovation interest melanoma mouse model nano nanoparticle nanoscale novel particle response scale up tumor

Address Adoption Adoptive Immunotherapy Antibodies Antigen-Presenting Cells Antigenic Specificity Antigens Autoantigens Autoimmune Diseases Autoimmunity Biological Biological Models Biomimetics CD28 gene CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes CD8B1 gene Cell Therapy Cells Cellular immunotherapy Chronic Clinical Complex Coupled Development Disease Effector Cell Engineering Formulation Frequencies Goals HLA-A2 Antigen Human Immunotherapeutic agent Immunotherapy In Vitro Lesion Ligands Magnetism Memory Metabolic Modeling Mus Patients Peptide/MHC Complex Phase I Clinical Trials Phenotype Preparation Process Production Protocols documentation Research Resistance Safety Signal Transduction System T cell therapy T-Lymphocyte Technology Time Translational Research Translations Tumor Antigens Virus Diseases Work antigen-specific T cells base cancer immunotherapy cancer therapy cost density design humanized mouse immunoengineering immunoregulation improved in vivo innovation interest melanoma mouse model nano nanoparticle nanoscale novel particle response scale up tumor

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项目摘要

TR&D 1 Summary: Adoptive cellular immunotherapy is a cancer treatment. In adoptive immunotherapy, T cells are isolated, manipulated, and stimulated in vitro, followed by expansion and administration into patients. Interest in this treatment is driven by impressive Phase I clinical trial results, in which the treatment has regressed large lesions, including treatment-resistant melanomas. The cost and complexity of treatment with adoptive immunotherapy have limited its use to research settings. In particular, T cell expansion requires prolonged culture. Autologous antigen presenting cells, or feeder cells, are a complex biologic that must be repeatedly assessed for safety and reliability, further increasing cost and labor. Immunotherapeutic strategies would benefit from effective “off-the-shelf” expansion platforms that reduce complexity and expense. In this TR&D we will engineer and optimize nanoscale artificial Antigen Presenting Cells, nano-aAPCs coupled to simplify, streamline, and scale-up production of T cells for adoptive immunotherapy. Our proposed studies will improve production of highly efficacious tumor antigen-specific CD8+ and CD4+ T cells for ACT by effectively increasing the frequency of antigen-specific cells and their functionality due to increased control of stimulating signals.

TR＆D 1摘要：收养细胞免疫疗法是一种癌症治疗。在适应性免疫疗法中，T细胞分离出来，在体外受到操纵和刺激，然后扩展和给予患者。对此感兴趣治疗是由令人印象深刻的I期临床试验结果驱动的，在该结果中，治疗已恢复大。病变，包括耐药黑色素瘤。自适应的成本和复杂性免疫疗法限制了其用于研究环境的用途。特别是，T细胞扩展需要延长文化。自体抗原呈递细胞或馈线细胞是一种复杂的生物学，必须重复评估安全性和可靠性，进一步增加成本和劳动力。免疫治疗策略会从有效的“现成”扩展平台中受益，这些平台降低了复杂性和费用。在这个tr＆d中将设计和优化纳米级人造抗原呈现细胞，纳米AAPC耦合以简化，简化T细胞进行自适应免疫疗法的扩大生产。我们提出的研究将改善产生高效的肿瘤抗原特异性CD8+和CD4+ T细胞，以有效地作用增加了抗原特异性细胞的频率及其功能性，由于增加了刺激的控制信号。