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

基本信息

批准号：
10645127
负责人：
JONATHAN P SCHNECK
金额：
$ 31.68万
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/10645127
关键词：
Acceleration 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 Separation 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 Proliferating Protocols documentation Research Resistance Signal Transduction System T cell therapy T-Lymphocyte Technology Time Translational Research Translations Tumor Antigens Virus Diseases Work antigen-specific T cells cancer immunotherapy cancer therapy cost density design humanized mouse immunoengineering immunoregulation improved in vivo innovation interest manufacturing scale-up melanoma mouse model nano nanoparticle nanoscale novel particle response safety assessment scale up tumor

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：过继性细胞免疫疗法是一种癌症治疗方法。在过继免疫疗法中，T 细胞被分离，在体外进行操作和刺激，然后进行扩展并给予患者。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，其中治疗已经大幅退步病变，包括难治性黑色素瘤。过继治疗的成本和复杂性免疫疗法限制了其在研究环境中的使用。特别是，T细胞扩增需要长时间文化。自体抗原呈递细胞或饲养细胞是一种复杂的生物制剂，必须重复评估安全性和可靠性，进一步增加成本和劳动力。免疫治疗策略将受益于有效的“现成”扩展平台，可降低复杂性和费用。在本次 TR&D 中，我们将设计和优化纳米级人工抗原呈递细胞、纳米 aAPC，以简化、简化并扩大用于过继免疫治疗的 T 细胞的生产。我们提出的研究将会改进通过有效地生产用于 ACT 的高效肿瘤抗原特异性 CD8+ 和 CD4+ T 细胞由于增加了刺激的控制，增加了抗原特异性细胞的频率及其功能信号。