Chimeric antigen receptor (CAR) T cell therapies have transformed outcomes for many patients with hematological malignancies. However, some patients do not respond to CAR T cell treatment, and adapting CAR T cells for solid and brain tumors has been met with many challenges including a hostile tumor microenvironment and poor CAR T cell persistence. Thus, it is unlikely that CAR T cell therapy alone will be sufficient for consistent, complete tumor clearance across cancer patients. Combinatorial therapies of CAR T cells and chemotherapeutics are a promising approach for overcoming this as chemotherapeutics could augment CAR T cells for improved anti-tumor activity or work in tandem with CAR T cells to clear tumors. Herein, we review efforts towards achieving successful CAR T cell and chemical drug combination therapies. We focus on combination therapies with approved chemotherapeutics as these will be more easily translated to the clinic, but also review non-approved chemotherapeutics and drug screens designed to reveal promising new CAR T cell and chemical drug combinations. Together, this review highlights the promise of CAR T cell and chemotherapy combinations with specific focus on how combinatorial therapy overcomes challenges faced by either monotherapy and supports the potential of this therapeutic strategy to improve outcomes for cancer patients. Significance Statement Improving currently available CAR T cell products via combinatorial therapy with chemotherapeutics has the potential to drastically expand the types of cancers and number of patients that could benefit from these therapies when neither alone has been sufficient to achieve tumor clearance. Herein, we provide a thorough review of the current efforts towards studying CAR T and chemotherapy combinatorial therapies and provide perspectives on optimal ways to identify new and effective combinations moving forward.

中文翻译：

---

组合 CAR T 细胞和化疗的治疗优势。


嵌合抗原受体 （CAR） T 细胞疗法改变了许多血液系统恶性肿瘤患者的预后。然而，一些患者对 CAR T 细胞治疗没有反应，并且使 CAR T 细胞适应实体瘤和脑瘤遇到了许多挑战，包括敌对的肿瘤微环境和 CAR T 细胞持久性差。因此，单独的 CAR T 细胞疗法不太可能足以在癌症患者中实现一致、完全的肿瘤清除。CAR T 细胞和化疗药物的组合疗法是克服这一问题的有前途的方法，因为化疗药物可以增强 CAR T 细胞以提高抗肿瘤活性，或与 CAR T 细胞协同作用以清除肿瘤。在本文中，我们回顾了为成功实现 CAR T 细胞和化学药物联合疗法所做的努力。我们专注于与已批准的化疗药物的联合疗法，因为这些疗法将更容易转化为临床，但也会审查未批准的化疗药物和药物筛选，旨在揭示有前景的新 CAR T 细胞和化学药物组合。总之，本综述强调了 CAR T 细胞和化疗联合疗法的前景，特别关注组合疗法如何克服任何一种疗法面临的挑战，并支持这种治疗策略改善癌症患者预后的潜力。意义声明 通过与化疗药物的联合疗法改进目前可用的 CAR T 细胞产品有可能大幅增加癌症类型和可以从这些疗法中受益的患者数量，而这两种疗法单独使用都不足以实现肿瘤清除。 在本文中，我们对当前研究 CAR T 和化疗组合疗法的努力进行了全面回顾，并就确定新的有效组合的最佳方法提供了展望。