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.

项目摘要/摘要 UCSF合成免疫学中心：重新编程免疫系统以对抗癌症的工具 免疫系统已成为一种与癌症作斗争的非常强大的工具。最大的 有效的药物经过设计的T细胞进行编程，以识别和杀死肿瘤细胞。尽管如此，我们的能力 工程师T细胞和其他免疫细胞并编程它们以执行新功能仍然相对原始。 除了用于治疗血液癌的汽车T细胞外，大多数工程细胞疗法都有风险，可能高度 有毒，不可靠且常常无效，尤其是那些试图靶向固体癌症的细胞疗法。我们 假设要实现工程免疫细胞疗法的承诺，我们必须首先转换细胞 工程为系统且可预测的过程；使用可靠的技术平台和 原则。我们的中心将专注于开发一组复杂的免疫工程平台，以解决 下一代细胞疗法的三个主要需求： 1）对癌症的智能识别 - 开发抗原模式识别电路，将免疫细胞直接引导至 最佳地识别实体瘤并区分正常组织交叉反应，以此为指导 基因表达模式的计算生物信息学分析。 2）克服肿瘤微环境 - 开发多种可以克服的细胞回路 或局部重塑免疫抑制肿瘤微环境，以促进高效的治疗 免疫细胞运输，增殖，持久性和杀人性肿瘤活性 3）用户控制和安全性 - 为了增加对这些强大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的沟通和控制活性的方法， 包括纳米/微粒和小分子。 为了实现这些目标，我们组装了UCSF合成免疫学中心，这是一个紧密整合的 跨学科团队包括合成生物学家，免疫学家，生物信息主义者，控制 工程师和材料科学家。该中心的产品将包括公开可用的零件工具包 和电池工程电路，快速电路组件的高通量平台，新的可编程 用于控制免疫细胞行为的纳米材料，可搜索的生物信息学数据库，以优化肿瘤 识别电路设计以及体内电路功能中的建模/原型制作的计算框架。 这些平台将有助于使免疫细胞工程变得更加可靠，可预测，有效，并且 安全的。