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

基本信息

批准号：
9790437
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/9790437
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 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

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，在过继性免疫疗法中，T 细胞被分离，在体外进行操作和刺激，然后扩展到患者体内。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。自体抗原呈递细胞或饲养细胞是一种复杂的生物学，必须重复培养。评估安全性和可靠性，进一步增加免疫治疗策略的成本和劳动力。受益于有效的“现成”扩展平台，可降低复杂性和费用。将设计和优化纳米级人工抗原呈递细胞、纳米 aAPC，以简化、我们提出的研究将改进用于过继免疫疗法的 T 细胞的生产流程和规模化。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。