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肉瘤及其他实体瘤中的细胞治疗

英文原题:Cellular therapies in sarcoma and other solid tumors.

PubMed 2025/05/05(内容时间) Curr Opin Oncol Q3 · IF 2.4(JCR 2025)

研究概要

在肉瘤领域,2024年8月afamitresgene autoleucel(afami-cel)获批用于滑膜肉瘤,标志着T细胞治疗的里程碑,在SPEARHEAD-1 2期试验中显示出39%的客观缓解率(ORR)和16.9个月的中位总生存期(OS)。

中文摘要

综述目的:CAR-T(CAR-T)细胞等过继细胞疗法已显示治疗血液系统恶性肿瘤的疗效,但由于肿瘤异质性、抗原特异性和免疫抑制性肿瘤微环境,其在实体瘤中的应用仍面临挑战。本综述概述肉瘤及其他实体恶性肿瘤细胞疗法的近期进展。最新发现:在肉瘤领域,阿法米赛(afami-cel)于2024年8月获批用于滑膜肉瘤,标志着T细胞疗法的一项里程碑;SPEARHEAD-1 II期试验显示其客观缓解率(ORR)为39%,中位总生存期(OS)为16.9个月。其他研究NY-ESO-1特异性T细胞受体工程化T(TCR-T)疗法治疗黏液样圆细胞脂肪肉瘤(MRCL)的试验也显示出令人鼓舞的缓解率。除肉瘤外,靶向胃肠道癌CLDN18.2、靶向胶质瘤GD2及靶向前列腺癌PSCA的CAR-T疗法,均显示出不同程度疗效,相关研究仍在进行。总结:临床上,这些疗法凸显了完善患者选择标准和优化抗原靶向的必要性。还须考虑毒性管理,因为细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)可能十分严重。未来研究应聚焦提高安全性和T细胞持久性,并完善生产流程以提升可及性和规模化能力。

展开英文摘要原文

PURPOSE OF REVIEW: While adoptive cell therapies such as chimeric antigen receptor T (CAR-T) cell have demonstrated efficacy in hematological malignancies, their success in solid tumors remains challenging due to tumor heterogeneity, antigen specificity, and the suppressive tumor microenvironment. This review aims to provide an overview of recent advancements in cellular therapies, in sarcomas and other solid malignancies. RECENT FINDINGS: In the field of sarcomas, the approval of afamitresgene autoleucel (afami-cel) for synovial sarcoma in Atoxiciugust 2024 marks a milestone in T cell therapy, demonstrating an objective response rate (ORR) of 39% and a median overall survival (OS) of 16.9 months in the SPEARHEAD-1 phase 2 trial. Other trials exploring NY-ESO-1 specific T-cell receptor-engineered T (TCR-T) therapies in myxoid round-cell liposarcoma (MRCL) have shown promising response rates. Beyond sarcomas, CAR-T therapies targeting CLDN18.2 in gastrointestinal cancers, GD2 in gliomas, and PSCA in prostate cancer have demonstrated varying degrees of efficacy, with ongoing research to date. SUMMARY: Clinically, these therapies highlight the need for improved patient selection criteria, and optimized antigen targeting. Toxicity management must also be taken into account, as cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) can be severe. Further studies should focus on improving safety and T cell persistence, and refining manufacturing processes to increase accessibility and scalability.

论文信息

作者
Dupont M、de Bernardi A、Vanacker H、Dufresne A、Brahmi M、Blay JY
第一作者单位
Medical Oncology Department, Centre Leon Berard, Lyon, France.France
文献类型
综述
期刊
Current opinion in oncology2025 Jul 1
原文标识
PubMed 40423031 · DOI 10.1097/CCO.0000000000001152