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用于急性髓系白血病的抗原特异性TCR-T细胞:现状与挑战

Antigen-Specific TCR-T Cells for Acute Myeloid Leukemia: State of the Art and Challenges.

作者信息

Kang Synat, Li Yisheng, Qiao Jingqiao, Meng Xiangyu, He Ziqian, Gao Xuefeng, Yu Li

机构信息

Department of Hematology and Oncology, International Cancer Center, Shenzhen Key Laboratory of Precision Medicine for Hematological Malignancies, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University Health Science Center, Shenzhen, China.

Central Laboratory, Shenzhen University General Hospital, Shenzhen, China.

出版信息

Front Oncol. 2022 Mar 9;12:787108. doi: 10.3389/fonc.2022.787108. eCollection 2022.

Abstract

The cytogenetic abnormalities and molecular mutations involved in acute myeloid leukemia (AML) lead to unique treatment challenges. Although adoptive T-cell therapies (ACT) such as chimeric antigen receptor (CAR) T-cell therapy have shown promising results in the treatment of leukemias, especially B-cell malignancies, the optimal target surface antigen has yet to be discovered for AML. Alternatively, T-cell receptor (TCR)-redirected T cells can target intracellular antigens presented by HLA molecules, allowing the exploration of a broader territory of new therapeutic targets. Immunotherapy using adoptive transfer of WT1 antigen-specific TCR-T cells, for example, has had positive clinical successes in patients with AML. Nevertheless, AML can escape from immune system elimination by producing immunosuppressive factors or releasing several cytokines. This review presents recent advances of antigen-specific TCR-T cells in treating AML and discusses their challenges and future directions in clinical applications.

摘要

急性髓系白血病(AML)中涉及的细胞遗传学异常和分子突变导致了独特的治疗挑战。尽管过继性T细胞疗法(ACT),如嵌合抗原受体(CAR)T细胞疗法,在白血病尤其是B细胞恶性肿瘤的治疗中已显示出有前景的结果,但尚未发现用于AML的最佳靶表面抗原。另外,T细胞受体(TCR)重定向的T细胞可以靶向由HLA分子呈递的细胞内抗原,从而能够探索更广泛的新治疗靶点领域。例如,采用WT1抗原特异性TCR-T细胞过继转移的免疫疗法在AML患者中已取得了积极的临床成效。然而,AML可通过产生免疫抑制因子或释放多种细胞因子来逃避免疫系统的清除。本文综述了抗原特异性TCR-T细胞在治疗AML方面的最新进展,并讨论了其在临床应用中的挑战和未来方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/36e3/8959347/7af183c6c6a1/fonc-12-787108-g001.jpg

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