文章：

肉瘤治疗中过继性细胞疗法的研究综述

Review of Adoptive Cellular Therapies for the Treatment of Sarcoma

原文发布日期：12 April 2025

DOI: 10.3390/cancers17081302

类型: Article

开放获取: 是

英文摘要：

Sarcomas are a heterogeneous group of malignancies with limited therapeutic options, particularly in the metastatic setting. Adoptive cellular therapies (ACTs), including tumor-infiltrating lymphocyte (TIL) therapy, chimeric antigen receptor (CAR) T-cell therapy, and T-cell receptor (TCR) gene-modified T-cell therapy, offer promising novel approaches for these refractory tumors. TIL-based therapy has demonstrated early efficacy in melanoma and myeloma, with ongoing trials exploring its role in sarcoma. CAR T-cell strategies targeting HER2, GD2, and B7-H3 antigens are in development, though challenges such as tumor microenvironment-mediated resistance and antigen escape remain significant. Engineered TCRs, particularly those targeting MAGE-A4 and NY-ESO-1, have shown promising clinical results in synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCLS), leading to the recent FDA approval of afamitresgene autoleucel (afami-cel) and letetresgene autoleucel (lete-cel). Despite encouraging preliminary data, ACT implementation faces barriers including limited antigen specificity, off-tumor toxicity, immune evasion, and manufacturing scalability. Future research will focus on optimizing lymphodepleting regimens, mitigating toxicity, enhancing in vivo persistence, and combining ACT with other therapeutic agents. As clinical trials expand, ACT holds the potential to revolutionize sarcoma treatment by offering durable, targeted therapies for previously refractory disease.

摘要翻译： 

肉瘤是一类异质性恶性肿瘤，治疗选择有限，尤其在转移性阶段。过继性细胞疗法（ACTs），包括肿瘤浸润淋巴细胞（TIL）疗法、嵌合抗原受体（CAR）T细胞疗法和T细胞受体（TCR）基因修饰T细胞疗法，为这类难治性肿瘤提供了前景广阔的新型治疗策略。基于TIL的疗法已在黑色素瘤和多发性骨髓瘤中显示出早期疗效，目前多项临床试验正在探索其在肉瘤治疗中的作用。针对HER2、GD2和B7-H3抗原的CAR T细胞策略正在开发中，但肿瘤微环境介导的耐药性和抗原逃逸等挑战仍然显著。工程化TCR疗法，特别是靶向MAGE-A4和NY-ESO-1的疗法，已在滑膜肉瘤（SS）和黏液样/圆细胞脂肪肉瘤（MRCLS）中显示出良好的临床效果，并促使阿法米替烯自体细胞（afami-cel）和来特替烯自体细胞（lete-cel）近期获得美国FDA批准。尽管初步数据令人鼓舞，但ACT的应用仍面临诸多障碍，包括抗原特异性有限、脱靶毒性、免疫逃逸以及规模化生产等问题。未来研究将聚焦于优化淋巴细胞清除方案、减轻毒性、增强体内持久性，以及将ACT与其他治疗药物联合应用。随着临床试验的扩展，ACT有望通过为既往难治性疾病提供持久、靶向的治疗方案，彻底改变肉瘤的治疗格局。

原文链接：

Review of Adoptive Cellular Therapies for the Treatment of Sarcoma