PDF(Pubmed)
Abstract：
Engineering immune cells to treat hematological malignancies has been a major focus of research since the first resounding successes of CAR-T-cell therapies in B-ALL. Several diseases can now be treated in highly therapy-refractory or relapsed conditions. Currently, a number of CD19- or BCMA-specific CAR-T-cell therapies are approved for acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), multiple myeloma (MM), and follicular lymphoma (FL). The implementation of these therapies has significantly improved patient outcome and survival even in cases with previously very poor prognosis. In this comprehensive review, we present the current state of research, recent innovations, and the applications of CAR-T-cell therapy in a selected group of hematologic malignancies. We focus on B- and T-cell malignancies, including the entities of cutaneous and peripheral T-cell lymphoma (T-ALL, PTCL, CTCL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), classical Hodgkin-Lymphoma (HL), Burkitt-Lymphoma (BL), hairy cell leukemia (HCL), and Waldenström\'s macroglobulinemia (WM). While these diseases are highly heterogenous, we highlight several similarly used approaches (combination with established therapeutics, target depletion on healthy cells), targets used in multiple diseases (CD30, CD38, TRBC1/2), and unique features that require individualized approaches. Furthermore, we focus on current limitations of CAR-T-cell therapy in individual diseases and entities such as immunocompromising tumor microenvironment (TME), risk of on-target-off-tumor effects, and differences in the occurrence of adverse events. Finally, we present an outlook into novel innovations in CAR-T-cell engineering like the use of artificial intelligence and the future role of CAR-T cells in therapy regimens in everyday clinical practice.
摘要：
自CAR-T细胞疗法在B-ALL中首次取得巨大成功以来，工程免疫细胞治疗血液恶性肿瘤一直是研究的主要焦点。现在可以在高度治疗难治性或复发性病症中治疗几种疾病。目前,许多CD19或BCMA特异性CAR-T细胞疗法被批准用于急性淋巴细胞白血病（ALL），弥漫性大B细胞淋巴瘤(DLBCL),套细胞淋巴瘤（MCL），多发性骨髓瘤（MM），和滤泡性淋巴瘤（FL）。即使在先前预后非常差的情况下，这些疗法的实施也显着改善了患者的预后和生存率。在这次全面审查中，我们介绍了研究的现状，最近的创新，以及CAR-T细胞疗法在一组选定的血液系统恶性肿瘤中的应用。我们专注于B细胞和T细胞恶性肿瘤，包括皮肤和外周T细胞淋巴瘤(T-ALL，PTCL,CTCL),急性髓系白血病(AML),慢性粒细胞白血病（CML），慢性淋巴细胞白血病（CLL），经典霍奇金淋巴瘤（HL），伯基特淋巴瘤(BL),毛细胞白血病（HCL），和Waldenström的巨球蛋白血症（WM）。虽然这些疾病是高度异质性的，我们强调了几种类似使用的方法(与既定的疗法相结合，健康细胞上的目标消耗)，用于多种疾病的靶标（CD30，CD38，TRBC1/2），和独特的功能，需要个性化的方法。此外，我们关注当前CAR-T细胞疗法在个体疾病和实体中的局限性，例如免疫受损的肿瘤微环境（TME），上靶-外肿瘤效应的风险，以及不良事件发生的差异。最后,我们对CAR-T细胞工程方面的创新进行了展望,如人工智能的使用,以及CAR-T细胞在日常临床实践治疗方案中的未来作用.
