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基于 T 细胞的血液系统恶性肿瘤免疫疗法,B 部分:过继细胞疗法的 SWOT 分析。

T-cell-based Immunotherapies for Haematological Cancers, Part B: A SWOT Analysis of Adoptive Cell Therapies.

机构信息

Barts Cancer Institute, Queen Mary University of London, London, U.K.;

Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, U.K.

出版信息

Anticancer Res. 2021 Mar;41(3):1143-1156. doi: 10.21873/anticanres.14871.

Abstract

Haematology has been at the forefront of cancer immunotherapy advancements. Allogeneic haematopoietic stem cell transplant (allo-HSCT) is one of the earliest forms of cancer immunotherapy and continues to cure thousands of patients. Donor lymphocyte infusion (DLI) increases allo-HSCT efficacy and reduces graft-versus-host disease (GVHD). In recent years, chimeric antigen receptor (CAR)-T-cells have been approved for the treatment of distinct haematologic malignancies, producing durable response in otherwise untreatable patients. New target antigen identification and technological advances have enabled the structural and functional evolution of CARs, broadening their applications. Despite successes, adoptive T-cell (ATC) therapies are expensive, can cause severe adverse reactions and their use is restricted to few patients. This review considers the current status and future perspectives of allogeneic transplant and donor lymphocytes, as well as novel ATC therapies, such as CAR-T-cells in haematological malignancies by analysing their strengths, weaknesses, opportunities, and threats (SWOT). The biological rationale for anti-cancer mechanisms and development; current clinical data in specific haematological malignancies; efficacy, toxicity, response and resistance profiles; novel strategies to improve these characteristics; and potential targets to enhance or expand the application of these therapies are discussed.

摘要

血液学一直处于癌症免疫治疗进展的前沿。异基因造血干细胞移植(allo-HSCT)是最早形式的癌症免疫疗法之一,至今仍治愈了数千名患者。供者淋巴细胞输注(DLI)可提高 allo-HSCT 的疗效并降低移植物抗宿主病(GVHD)的发生。近年来,嵌合抗原受体(CAR)-T 细胞已被批准用于治疗特定的血液恶性肿瘤,为原本无法治疗的患者带来持久的缓解。新的靶抗原鉴定和技术进步使 CAR 的结构和功能得到了发展,拓宽了它们的应用范围。尽管取得了成功,但过继性 T 细胞(ATC)疗法昂贵,可能会引起严重的不良反应,并且其应用仅限于少数患者。本综述通过分析其优势、劣势、机会和威胁(SWOT),考虑了同种异体移植和供者淋巴细胞以及新型 ATC 疗法(如 CAR-T 细胞)在血液恶性肿瘤中的现状和未来前景,讨论了其抗癌机制和发展的生物学原理;特定血液恶性肿瘤的当前临床数据;疗效、毒性、反应和耐药谱;改善这些特征的新策略;以及增强或扩大这些疗法应用的潜在靶点。

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