Cancer immunotherapies rely on one or few specific tumour-associated antigens. However, the adaptive immune system relies on a large and diverse repertoire of antibodies for antigen recognition. Here we report the development and applicability of libraries of immune cells displaying diverse repertoires of chimaeric antigen receptors (CARs) that can recognize non-self antigens and display antigen-dependent clonal expansion, with the expanded population of tumour-specific effector cells leading to long-lasting antitumour responses in mouse models of epithelial tumours. The intravenous injection of synthetic libraries of murine CARs on TET2^– T cells led to robust immunological memory and the recognition of mutated or evolved tumours, owing to the maintenance of CAR diversity. Off-the-shelf libraries of 10⁶ murine or human CAR clones displayed on genetically modified human NK-92 cancer cells completely eliminated established tumours in mice with murine xenografts and patient-derived xenografts. Synthetically generated CAR libraries may aid the discovery of new CARs and the development of immunotherapies.

癌症免疫疗法依赖于一种或几种特定的肿瘤相关抗原。然而，适应性免疫系统依赖于大量多样的抗体来识别抗原。在这里，我们报告了免疫细胞文库的发展和适用性，这些免疫细胞展示了多种嵌合抗原受体 (CAR) 库，可以识别非自身抗原并展示抗原依赖性克隆扩增，肿瘤特异性效应细胞群的扩大导致长期-上皮肿瘤小鼠模型中的持久抗肿瘤反应。在TET2上静脉注射小鼠 CAR 的合成文库^–由于 CAR 多样性的维持，T 细胞导致了强大的免疫记忆和对突变或进化肿瘤的识别。在转基因人类 NK-92 癌细胞上展示的 10 ^{6 个}小鼠或人类 CAR 克隆的现成文库使用小鼠异种移植物和患者来源的异种移植物完全消除了小鼠体内已形成的肿瘤。合成生成的 CAR 库可能有助于发现新的 CAR 和开发免疫疗法。