Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.
Division of Blood and Marrow Transplantation and Cellular Therapeutics, Center for Cancer and Blood Disorders, Children's Hospital Colorado, Aurora, CO, USA.
Immunol Rev. 2019 Jul;290(1):100-113. doi: 10.1111/imr.12794.
Advances in the development of immunotherapies have offered exciting new options for the treatment of malignant diseases that are refractory to conventional cytotoxic chemotherapies. The adoptive transfer of T cells expressing chimeric antigen receptors (CARs) has demonstrated dramatic results in clinical trials and highlights the promise of novel immune-based approaches to the treatment of cancer. As experience with CAR T cells has expanded with longer follow-up and to a broader range of diseases, new obstacles have been identified which limit the potential lifelong benefits of CAR T cell therapy. These obstacles highlight not only the gaps in knowledge of the optimal clinical application of this "living drug", but also gaps in our understanding of the fundamental biology of CAR T cells themselves. In this review, we discuss the obstacles facing CAR T cell therapy, how these relate to our current understanding of CAR T cell biology and approaches to enhance the clinical efficacy of this therapy.
免疫疗法的进展为治疗对传统细胞毒化疗耐药的恶性疾病提供了令人兴奋的新选择。嵌合抗原受体 (CAR) 表达 T 细胞的过继转移在临床试验中取得了显著效果，突显了新型免疫治疗方法治疗癌症的前景。随着 CAR T 细胞治疗经验的扩展，包括更长时间的随访和更广泛的疾病范围，已经确定了新的障碍，这些障碍限制了 CAR T 细胞治疗的潜在终身益处。这些障碍不仅凸显了我们对这种“活药物”最佳临床应用的知识差距，也凸显了我们对 CAR T 细胞本身的基础生物学的理解差距。在这篇综述中，我们讨论了 CAR T 细胞治疗面临的障碍，以及这些障碍如何与我们目前对 CAR T 细胞生物学的理解以及增强这种治疗方法的临床疗效的方法相关。
