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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：细胞免疫疗法是一种癌症治疗方法。在过继免疫治疗中，T细胞被分离，操作，并在体外刺激，然后扩增并施用于患者。来面试这份治疗是由令人印象深刻的I期临床试验结果驱动的，在该试验中，病变，包括难治性黑素瘤。治疗的成本和复杂性与收养免疫疗法限制了其在研究环境中的使用。特别是，T细胞扩增需要延长文化自体抗原提呈细胞或饲养细胞是一种复杂的生物学物质，必须反复地评估安全性和可靠性，进一步增加成本和劳动力。免疫策略将受益于有效的“现成”扩展平台，可降低复杂性和成本。在这个TR&D中，我们将设计和优化纳米人工抗原呈递细胞，纳米aAPC耦合，以简化，用于过继免疫治疗T细胞的流线型和规模化生产。我们建议的研究将改善通过有效地产生用于ACT的高效肿瘤抗原特异性CD8+和CD4+ T细胞，由于增加了对刺激的控制，信号.