School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
Department of Pediatric Surgery, University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany.
Front Immunol. 2024 Jun 19;15:1383894. doi: 10.3389/fimmu.2024.1383894. eCollection 2024.
Chimeric antigen receptor (CAR) T cell therapy has effectively complemented the treatment of advanced relapsed and refractory hematological cancers. The remarkable achievements of CD19- and BCMA-CAR T therapies have raised high expectations within the fields of hematology and oncology. These groundbreaking successes are propelling a collective aspiration to extend the reach of CAR therapies beyond B-lineage malignancies. Advanced CAR technologies have created a momentum to surmount the limitations of conventional CAR concepts. Most importantly, innovations that enable combinatorial targeting to address target antigen heterogeneity, using versatile adapter CAR concepts in conjunction with recent transformative next-generation CAR design, offer the promise to overcome both the bottleneck associated with CAR manufacturing and patient-individualized treatment regimens. In this comprehensive review, we delineate the fundamental prerequisites, navigate through pivotal challenges, and elucidate strategic approaches, all aimed at paving the way for the future establishment of multitargeted immunotherapies using universal CAR technologies.
嵌合抗原受体 (CAR) T 细胞疗法有效地补充了晚期复发和难治性血液系统癌症的治疗方法。CD19 和 BCMA-CAR T 疗法的显著成就，在血液学和肿瘤学领域引起了高度关注。这些突破性的成功，推动了将 CAR 疗法的应用范围从 B 细胞恶性肿瘤扩展到其他领域的集体愿望。先进的 CAR 技术为克服传统 CAR 概念的局限性创造了动力。最重要的是，创新的组合靶向策略可以解决靶抗原异质性问题，使用多功能适配器 CAR 概念，并结合最近的变革性下一代 CAR 设计，有望克服与 CAR 制造和个体化患者治疗方案相关的瓶颈。在这篇全面的综述中，我们阐述了基本前提、关键挑战，并阐明了战略方法，旨在为未来使用通用 CAR 技术建立多靶点免疫疗法铺平道路。
