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INSPIRED 研讨会第 4B 部分:CAR-T 细胞相关研究——已确立的发现与未来优先方向

英文原题:INSPIRED Symposium Part 4B: Chimeric Antigen Receptor T Cell Correlative Studies-Established Findings and Future Priorities.

查看英文原题

INSPIRED Symposium Part 4B: Chimeric Antigen Receptor T Cell Correlative Studies-Established Findings and Future Priorities.

PubMed 2023/10/18(内容时间) Transplant Cell Ther Q1 · IF 4.7(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)T细胞疗法改变了B细胞恶性肿瘤的治疗格局,全球监管机构已批准多种CAR-T 产品用于不同适应证,但仍需大量工作进一步优化这些疗法。2023年3月,一组CAR-T 领域专家齐聚美国马里兰州贝塞斯达美国国立卫生研究院,参加“儿童CAR-T 免疫治疗洞见:近期进展与未来方向”(INSPIRED)研讨会,为未来数年确定关键研究领域。第4B场会议讨论了应纳入未来临床试验和真实世界研究的关联性研究。确定的活跃研究方向包括:(1)优化CAR-T 产品制备;(2)确保CAR-T 给药前充分进行淋巴细胞清除;(3)克服肿瘤微环境中的免疫调节细胞和肿瘤基质,尤其是在实体瘤中;(4)理解导致CAR-T 免疫治疗耐药的肿瘤内在特征;(5)发现可预测治疗耐药、疗效持久性或免疫相关不良事件的生物标志物。本文综述既往已发表临床试验和真实世界研究结果,总结上述各方面目前的认识,并提出作者认为有助于加深对CAR-T 疗法理解、最终改善患者结局的未来研究优先事项。

展开英文摘要原文

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.

论文信息

作者
Ligon JA、Ramakrishna S、Ceppi F、Calkoen FGJ、Diorio C、Davis KL、Jacoby E、Gottschalk S
单位
Department of Pediatrics, Division of Hematology/Oncology, University of Florida, Gainesville, Florida; University of Florida Health Cancer Center, Gainesville, Florida. Electronic address: john.ligon@ufl.edu.
文献类型
综述 · 美国 NIH 资助研究
期刊
Transplantation and cellular therapy2024 Feb
原文标识
PubMed 37863355 · DOI 10.1016/j.jtct.2023.10.012