Chimeric antigen receptor (CAR) T cell therapy is currently approved for treatment of refractory B-cell malignancies. Response rates in these diseases are impressive by historical standards, but most patients do not have a durable response and there remains room for improvement. To date, CAR T cell activity has been even more limited in solid malignancies. These limitations are thought to be due to several pathways of resistance to CAR T cells, including cell-intrinsic mechanisms and the immunosuppressive tumor microenvironment. In this review, we discuss current experimental strategies that combine small molecules and monoclonal antibodies with CAR T cells to overcome these resistance mechanisms. We describe the biological rationale, pre-clinical data and clinical trials in progress that test the efficacy and safety of these combinations.

嵌合抗原受体 (CAR) T 细胞疗法目前被批准用于治疗难治性 B 细胞恶性肿瘤。以历史标准衡量，这些疾病的反应率令人印象深刻，但大多数患者没有持久的反应，仍有改善的空间。迄今为止，CAR T 细胞活性在实体恶性肿瘤中更加有限。这些限制被认为是由于对 CAR T 细胞的几种抗性途径，包括细胞内在机制和免疫抑制性肿瘤微环境。在这篇综述中，我们讨论了目前将小分子和单克隆抗体与 CAR T 细胞相结合以克服这些耐药机制的实验策略。我们描述了测试这些组合的有效性和安全性的生物学原理、临床前数据和正在进行的临床试验。