肿瘤细胞治疗研究
英文原题：Current developments in T-cell receptor therapy for acute myeloid leukemia.
T 细胞受体（TCR）疗法是治疗癌症的一种有前景的方式，其中大量努力正投向急性髓系白血病（AML）这一尤其具有挑战性的疾病。
T细胞受体（TCR）疗法是有希望的癌症治疗方式，目前大量研究正聚焦于急性髓系白血病（AML），这一疾病治疗尤其困难。靶向单一表面抗原的嵌合抗原受体（CAR）T细胞已在B细胞淋巴细胞白血病、淋巴瘤和多发性骨髓瘤中显示显著疗效。然而，由于白血病免疫表型及表面抗原靶点广泛异质，且这些靶点也存在于正常髓系细胞，AML为CAR-T疗效带来重大障碍。TCR疗法是不断发展的细胞疗法领域，可靶向由HLA分子呈递的细胞内抗原肽。AML TCR疗法正通过临床前研究和成功临床试验快速发展。本综述聚焦AML治疗靶抗原、TCR识别所用的多种方法和策略，以及临床前TCR-T细胞开发。文章还讨论用于改善功能疗效、缓解安全性顾虑及克服HLA限制的创新分子设计，并重点介绍针对重要抗原早期临床试验的具体结果，包括Wilms肿瘤基因1、黑色素瘤优先表达抗原及次要组织相容性抗原HA-1。总之，本综述强调TCR疗法有望成为AML免疫治疗不可或缺的组成部分。
T-cell receptor (TCR) therapies are a promising modality for the treatment of cancers, with significant efforts being directed toward acute myeloid leukemia (AML), a particularly challenging disease. Chimeric antigen receptor (CAR) T cells targeting single surface antigens have shown remarkable efficacy for B-cell lymphoblastic leukemia, lymphomas, and multiple myeloma. However, AML presents formidable obstacles to the effectiveness of CAR T cells because of the widespread expression of heterogenous leukemia immunophenotypes and surface antigen targets additionally present on normal myeloid cells. TCR therapies are an evolving field of cell therapies that allow targeting intracellular antigenic peptides presented via HLA molecules. The development of TCR therapy for AML is progressing rapidly through preclinical research and successful clinical trials. This review specifically explores the antigens targeted in AML, the diverse methodologies and strategies used in TCR identification, and preclinical TCR T-cell development. The review also discusses innovative molecular designs to improve functional efficacy, mitigate safety concerns, and overcome HLA restrictions. Specific outcomes of early clinical trials targeting important antigens Wilms tumor gene 1, preferentially expressed antigen in melanoma, and minor histocompatibility antigen HA-1 are also highlighted. Ultimately, this review underscores why TCR therapy is poised to become an indispensable component of AML immunotherapy.
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