UCSF Center for Synthetic Immunology: Tools to Reprogram the Immune System to Combat Cancer

加州大学旧金山分校合成免疫学中心：重新编程免疫系统以对抗癌症的工具

• 批准号: 10598362
• 负责人: WENDELL A LIM
• 金额: $ 5.93万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-24 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10598362
• 关键词: Address; Antigens; Bioinformatics; Cell Therapy; Cells; Cellular immunotherapy; Databases; Engineering; Gene Expression Profiling; Goals; Hematopoietic Neoplasms; Immune; Immune system; Immunologist; Immunotherapeutic agent; Malignant Neoplasms; Modeling; Normal tissue morphology; Pattern Recognition; Process; Safety; Scientist; Solid; Solid Neoplasm; Synthetic immunology; Technology; blood treatment; cell behavior; cell transformation; cellular engineering; chimeric antigen receptor T cells; combat; computer framework; design; engineered T cells; immunoengineering; in vivo; nano; nanomaterials; neoplastic cell; next generation; programs; prototype; small molecule; tool; trafficking; tumor; tumor microenvironment

Project Summary/Abstract UCSF Center for Synthetic Immunology: Tools to Reprogram the Immune System to Combat Cancer The immune system has emerged as an extraordinarily powerful tool for combating cancer. One of the most potent agents are engineered T cells programmed to recognize and kill tumor cells. Nonetheless, our ability to engineer T cells and other immune cells and program them to execute new functions remains relatively primitive. Aside from CAR T cells for treatment of blood cancers, most engineered cell therapies are risky, potentially highly toxic, unreliable and often ineffective, especially those cell therapies that attempt to target solid cancers. We hypothesize that to fulfil the promise of engineered immune cell therapies, we must first transform cell engineering into a systematic and predictable process; one that uses reliable technology platforms and principles. Our center will focus on developing a set of sophisticated immune engineering platforms that address three major needs in next-generation cell therapies: 1) Smart recognition of cancer – develop antigen-pattern recognition circuits that direct immune cells to optimally recognize solid tumors and discriminate against normal tissue crossreaction, guided by computational bioinformatic analysis of gene expression patterns. 2) Overcoming the tumor microenvironment – develop multiple classes of cellular circuits that can overcome or locally remodel immune-suppressive tumor microenvironments to promote highly efficient therapeutic immune cell trafficking, proliferation, persistence, and tumor-killing activity 3) User-control and safety – to increase control over and safety of these powerful engineered cells, we will develop a suite of ways to communicate with and control the activity of engineered immune cells in vivo, including nano/microparticles and small molecules. To achieve these goals, we have assembled the UCSF Center for Synthetic Immunology, a tightly integrated interdisciplinary team that encompasses synthetic biologists, immunologists, bio-informaticists, control engineers, and materials scientists. The products of this center will include publicly available toolkits of parts and circuits for cell engineering, high-throughput platforms for rapid circuit assembly, new programmable nanomaterials for controlling immune cell behavior, searchable bioinformatic databases for optimization of tumor recognition, and computational frameworks for circuit design and for modeling/prototyping in vivo circuit function. These platforms will help to advance immune cell engineering to be far more reliable, predictable, effective and safe.

项目概要/摘要 加州大学旧金山分校合成免疫学中心：重新编程免疫系统以对抗癌症的工具 免疫系统已成为对抗癌症最强大的工具之一。 有效的药物是经过编程的 T 细胞，可以识别和杀死肿瘤细胞，但我们的能力还不够。 对 T 细胞和其他免疫细胞进行改造并对其进行编程以执行新功能仍然相对原始。 除了用于治疗血癌的 CAR T 细胞外，大多数工程细胞疗法都存在风险，可能风险很高 有毒、不可靠且常常无效，尤其是那些试图针对实体癌的细胞疗法。 追求的是，​​为了实现工程免疫细胞疗法的承诺，我们必须首先转化细胞 工程化为一个系统化、可预测的流程； 我们的中心将专注于开发一套复杂的免疫工程平台来解决这一问题。 下一代细胞疗法的三大需求： 1) 智能识别癌症——开发抗原模式识别电路，引导免疫细胞 在以下指导下，最佳地识别实体瘤并区分正常组织交叉反应 基因表达模式的计算生物信息分析。 2) 克服肿瘤微环境——开发多类可以克服肿瘤微环境的细胞回路 或局部重塑免疫抑制肿瘤微环境以促进高效治疗 免疫细胞运输、增殖、持久性和肿瘤杀伤活性 3) 用户控制和安全——为了增强对这些强大的工程细胞的控制和安全性，我们将 开发一套与体内工程免疫细胞通信并控制其活性的方法， 包括纳米/微米颗粒和小分子。 为了实现这些目标，我们组建了 UCSF 合成免疫学中心，这是一个紧密集成的中心 跨学科团队，包括合成生物学家、免疫学家、生物信息学家、控制学家 该中心的产品将包括公开可用的零件工具包。 和用于细胞工程的电路、用于快速电路组装的高通量平台、新的可编程 用于控制免疫细胞行为的纳米材料、用于优化肿瘤的可搜索生物信息数据库 用于电路设计和体内电路功能建模/原型设计的识别和计算框架。 这些平台将有助于推进免疫细胞工程变得更加可靠、可预测、有效和 安全的。