肿瘤细胞治疗研究
英文原题：Neoantigen-specific TCR-T cell-based immunotherapy for acute myeloid leukemia.
源自非同义体细胞突变的新抗原仅限于恶性细胞，因此被认为是基于T细胞受体（TCR）的免疫治疗的理想靶点。
源自非同义体细胞突变的新抗原仅限于恶性细胞，因此被认为是基于T细胞受体（TCR）的免疫治疗的理想靶点。过继转移携带新抗原特异性TCR的T细胞表现出优先靶向肿瘤细胞的能力，同时对正常细胞无害。已在体外鉴定出针对AML细胞表达的新抗原的高亲和力TCR，并通过异种移植小鼠模型进行了验证。这些新抗原特异性TCR-T细胞的临床前研究正在进行中，作为安全有效的疗法具有巨大前景。此外，靶向肿瘤相关抗原的TCR免疫疗法已用于治疗AML的早期临床试验，并显示出令人鼓舞的抗白血病效果。这些临床经验支持应用专门设计用于识别新抗原的TCR-T细胞。在本综述中，我们将详细描述AML中已验证的新抗原，描述鉴定新抗原特异性TCR的策略，并讨论新抗原特异性T细胞免疫疗法在AML中的潜力。
Neoantigens derived from non-synonymous somatic mutations are restricted to malignant cells and are thus considered ideal targets for T cell receptor (TCR)-based immunotherapy. Adoptive transfer of T cells bearing neoantigen-specific TCRs exhibits the ability to preferentially target tumor cells while remaining harmless to normal cells. High-avidity TCRs specific for neoantigens expressed on AML cells have been identified in vitro and verified using xenograft mouse models. Preclinical studies of these neoantigen-specific TCR-T cells are underway and offer great promise as safe and effective therapies. Additionally, TCR-based immunotherapies targeting tumor-associated antigens are used in early-phase clinical trials for the treatment of AML and show encouraging anti-leukemic effects. These clinical experiences support the application of TCR-T cells that are specifically designed to recognize neoantigens. In this review, we will provide a detailed profile of verified neoantigens in AML, describe the strategies to identify neoantigen-specific TCRs, and discuss the potential of neoantigen-specific T-cell-based immunotherapy in AML.
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