肿瘤细胞治疗研究
英文原题：Supercharged chimeric antigen receptor T cells in solid tumors.
嵌合抗原受体（CAR）T细胞已在治疗部分血液系统恶性肿瘤中取得成功，但其在实体瘤中的活性相对有限。
嵌合抗原受体（CAR）T细胞已在治疗部分血液系统恶性肿瘤中展现出成功，但其在实体瘤中的活性相对有限。治疗实体瘤所面临的特定挑战包括：在肿瘤部位内的转运和分布、克服免疫抑制性肿瘤微环境（TME），以及鉴定广泛表达且对肿瘤生物学不可或缺的抗原靶点。在本期JCI中，Tian等人描述了使用双顺反子CAR T细胞靶向神经母细胞瘤中表达的多种抗原，以克服抗原异质性。将这一方法与增强T细胞转运和防止TME中获得性功能障碍的干预措施相结合，可能为CAR T细胞治疗实体瘤的临床实施带来期待已久的突破。
Chimeric antigen receptor (CAR) T cells have demonstrated success in treating select hematological malignancies, but their activity in solid tumors has been comparably modest. Challenges specific to treating solid tumors include trafficking and distribution throughout the tumor site, overcoming the immunosuppressive tumor microenvironment (TME), and identifying antigenic targets that are widely expressed and indispensable to tumor biology. In this issue of the JCI, Tian et al. describe the use of bicistronic CAR T cells that target multiple antigens expressed in neuroblastoma to overcome antigenic heterogeneity. Combining this approach with interventions that enhance T cell trafficking and prevent acquired dysfunction in the TME may lead to a long-awaited breakthrough in the clinical implementation of CAR T cells for the treatment of solid tumors.
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