Department of Pediatrics, Division of Hematology/Oncology, University of Florida, Gainesville, Florida; University of Florida Health Cancer Center, Gainesville, Florida.
Stanford Center for Cancer Cell Therapy, Stanford University School of Medicine, Stanford, California; Department of Pediatrics, Stanford University, Stanford, California.
Transplant Cell Ther. 2024 Feb;30(2):155-170. doi: 10.1016/j.jtct.2023.10.012. Epub 2023 Oct 18.
Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of B cell malignancies, with multiple CAR T cell products approved for numerous indications by regulatory agencies worldwide. However, significant work remains to be done to enhance these treatments. In March 2023, a group of experts in CAR T cell therapy assembled at the National Institutes of Health in Bethesda, Maryland at the Insights in Pediatric CAR T Cell Immunotherapy: Recent Advances and Future Directions (INSPIRED) Symposium to identify key areas for research for the coming years. In session 4B, correlative studies to be incorporated into future clinical trials and real-world settings were discussed. Active areas of research identified included (1) optimizing CAR T cell product manufacturing; (2) ensuring adequate lymphodepletion prior to CAR T cell administration; (3) overcoming immunoregulatory cells and tumor stroma present in the tumor microenvironment, particularly in solid tumors; (4) understanding tumor intrinsic properties that lead to CAR T cell immunotherapy resistance; and (5) uncovering biomarkers predictive of treatment resistance, treatment durability, or immune-related adverse events. Here we review the results of previously published clinical trials and real-world studies to summarize what is currently known about each of these topics. We then outline priorities for future research that we believe will be important for improving our understanding of CAR T cell therapy and ultimately leading to better outcomes for patients.
嵌合抗原受体 (CAR) T 细胞疗法彻底改变了 B 细胞恶性肿瘤的治疗方法，全球多个监管机构已批准多种 CAR T 细胞产品用于多种适应症。然而，仍需要做大量工作来增强这些治疗方法。2023 年 3 月，一群 CAR T 细胞治疗专家齐聚马里兰州贝塞斯达的美国国立卫生研究院，参加了儿童 CAR T 细胞免疫疗法的见解：近期进展和未来方向 (INSPIRED) 研讨会，以确定未来几年的研究重点。在第 4B 环节，讨论了将纳入未来临床试验和真实环境的相关研究。确定的研究活跃领域包括：(1) 优化 CAR T 细胞产品制造；(2) 在 CAR T 细胞给药前确保充分的淋巴耗竭；(3) 克服肿瘤微环境中存在的免疫调节细胞和肿瘤基质，特别是在实体瘤中；(4) 了解导致 CAR T 细胞免疫治疗耐药的肿瘤内在特性；(5) 揭示预测治疗耐药、治疗持久性或免疫相关不良事件的生物标志物。在这里，我们回顾了之前发表的临床试验和真实世界研究的结果，总结了目前对每个主题的了解。然后，我们概述了未来研究的优先事项，我们认为这些研究对于加深我们对 CAR T 细胞治疗的理解并最终为患者带来更好的结果非常重要。
