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

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.

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.