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

项目总结/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 免疫系统已经成为对抗癌症的非常强大的工具。一个最 有效的药物是被编程为识别和杀死肿瘤细胞的工程化T细胞。尽管如此，我们的能力， 改造T细胞和其他免疫细胞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是有风险的，可能非常高。 有毒、不可靠且通常无效，尤其是那些试图靶向实体癌的细胞疗法。我们 假设为了实现工程免疫细胞疗法的前景，我们必须首先转化细胞， 将其设计成一个系统化和可预测的过程;一个使用可靠的技术平台， 原则我们的中心将专注于开发一套复杂的免疫工程平台， 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，指导免疫细胞 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学分析。 2)克服肿瘤微环境-开发多种类型的细胞回路， 或局部重塑免疫抑制性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)用户控制和安全性-为了提高对这些强大的工程细胞的控制和安全性，我们将 开发一套方法来与体内工程免疫细胞沟通并控制其活性， 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，这是一个紧密整合的 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 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 和电路的细胞工程，高通量平台的快速电路组装，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学数据库 识别和用于电路设计和用于体内电路功能建模/原型化的计算框架。 这些平台将有助于推动免疫细胞工程变得更加可靠，可预测，有效和安全。 安全了

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.