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

项目摘要/摘要 加州大学旧金山分校合成免疫学中心：重组免疫系统以抗击癌症的工具 免疫系统已经成为抗击癌症的非常强大的工具。其中最 有效的药物是经过改造的T细胞，可以识别和杀死肿瘤细胞。尽管如此，我们有能力 设计T细胞和其他免疫细胞并对它们进行编程以执行新功能仍然是相对原始的。 除了CAR T细胞用于治疗血癌外，大多数基因工程细胞疗法都是有风险的，潜在风险很高 有毒、不可靠，而且往往无效，特别是那些试图针对实体癌的细胞疗法。我们 假设为了实现工程免疫细胞疗法的承诺，我们必须首先转化细胞 将工程设计为系统和可预测的过程；使用可靠的技术平台和 原则。我们的中心将专注于开发一套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)癌症的智能识别-开发抗原模式识别电路，引导免疫细胞 最佳识别实体肿瘤并区分正常组织交叉反应，由 基因表达模式的计算生物信息学分析。 2)克服肿瘤微环境-发展多种类型的细胞电路，可以克服 或局部重塑免疫抑制的肿瘤微环境，以促进高效治疗 免疫细胞的运输、增殖、持续与肿瘤杀伤活性 3)用户控制和安全-为了加强对这些功能强大的工程电池的控制和安全性，我们将 开发一套在体内与工程免疫细胞交流和控制其活性的方法， 包括纳米/微米粒子和小分子。 为了实现这些目标，我们组建了加州大学旧金山分校合成免疫学中心，一个紧密整合的 由合成生物学家、免疫学家、生物信息学家、控制学家组成的跨学科团队 工程师和材料科学家。该中心的产品将包括公开提供的零部件工具包 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 安然无恙。

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.