肿瘤细胞治疗研究
英文原题：Chimeric Antigen Receptor T cell Therapy and the Immunosuppressive Tumor Microenvironment in Pediatric Sarcoma.
Chimeric Antigen Receptor T cell Therapy and the Immunosuppressive Tumor Microenvironment in Pediatric Sarcoma.
肉瘤是一组多样化的骨和软组织肿瘤，占儿童癌症的10%以上。
肉瘤是一组多样化的骨和软组织肿瘤，占儿童癌症的10%以上。对于难治性、复发性或转移性疾病的儿童，预后尤其差。CAR-T（CAR T）细胞是一种令人兴奋的过继性细胞疗法，可能为这些儿童带来新的希望。在早期试验中，一些儿童肉瘤患者已取得有希望的结果。然而，尽管靶向肿瘤抗原显著表达，许多儿童仍未获益。CAR T细胞疗法在肉瘤和其他实体瘤中的成功受到免疫抑制性肿瘤微环境（TME）的限制。在这篇综述中，我们提供目前正在儿童肉瘤临床试验中测试的CAR T细胞疗法的最新进展，包括针对表达HER2、NY-ESO、GD2、EGFR、GPC3、B7-H3和MAGE-A4的肿瘤的疗法。我们还概述了处于临床前开发中的有前景的新型CAR T细胞。最后，我们讨论正在用于克服实体瘤中肿瘤介导免疫抑制的策略；这些策略有可能改善肉瘤儿童CAR T细胞疗法的临床结局。
Sarcomas are a diverse group of bone and soft tissue tumors that account for over 10% of childhood cancers. Outcomes are particularly poor for children with refractory, relapsed, or metastatic disease. Chimeric antigen receptor T (CAR T) cells are an exciting form of adoptive cell therapy that potentially offers new hope for these children. In early trials, promising outcomes have been achieved in some pediatric patients with sarcoma. However, many children do not derive benefit despite significant expression of the targeted tumor antigen. The success of CAR T cell therapy in sarcomas and other solid tumors is limited by the immunosuppressive tumor microenvironment (TME). In this review, we provide an update of the CAR T cell therapies that are currently being tested in pediatric sarcoma clinical trials, including those targeting tumors that express HER2, NY-ESO, GD2, EGFR, GPC3, B7-H3, and MAGE-A4. We also outline promising new CAR T cells that are in pre-clinical development. Finally, we discuss strategies that are being used to overcome tumor-mediated immunosuppression in solid tumors; these strategies have the potential to improve clinical outcomes of CAR T cell therapy for children with sarcoma.
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