靶向CD19的T细胞治疗恶性血液疾病到目前为止的临床经验

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CD19-Targeted T Cells for Hematologic Malignancies: Clinical Experience to Date.

Recently, immunotherapy for cancer has begun to garner traction with encouraging results in a number of malignancies. Included within this arena has been the genetic engineering of autologous T cells with chimericantigen receptors (CARs) against tumor target. The majority of this experience has included the use of CAR T cells directed against CD19 for B-cell hematologic malignancies. The most striking efficacy to date with CAR T cells directed against CD19 has been in relapsed and refractory B-cell acute lymphoblastic leukemia, with the overwhelming majority of patients experiencing complete remissions. In addition, single-center and largely early-phase studies have demonstrated responses in patients with varying histologic findings of relapsed and refractory B-cell non-Hodgkin lymphoma. The favorable response rates seen with this technology have been tempered by the high risk of toxicity, particularly in the form of cytokine-release syndrome and neurotoxicity. Agents such as tocilizumab and corticosteroids have been used to treat these toxicities. The current state of the science includes strategies to circumvent and treat toxicity, manufacturing, and study of later-generation CAR constructs with the intention of improving efficacy and development of CARs against other tumor targets for both hematologic and solid tumor malignancies. The observation of an early efficacy ensures further integration and development of this modality into future immunotherapeutic strategies for various cancers.

靶向CD19的T细胞治疗恶性血液疾病到目前为止的临床经验

最近，对于一些恶性肿瘤的治疗，免疫治疗开始取得了一些激动人心的结果。在这个范畴中，就有一个基因修饰的靶向肿瘤抗原的嵌合抗原受体修饰的自体T细胞技术。主要的成果经验包括使用靶向CD19的CAR-T细胞治疗B细胞恶性血液病。到目前为止，靶向CD19的CAR-T细胞取得最大的成果是在复发性/难治性B细胞急性淋巴细胞白血病的治疗中，绝大多数患者能够取得一个完全的环节率。此外，单中心和早期的研究发现，复发性难治性非霍奇金淋巴瘤患者具有不同的组织学表现。这个技术能够取得的有效性会被毒副作用所影响，尤其是细胞因子释放综合症和神经毒性。托珠单抗和糖皮质激素已经被用于对抗这些副反应。目前对于这种技术的发展，主要包括一些规避和治疗毒性的策略，制造和研究新一代CAR-T以提高疗效和发展CAR-T技术对其他肿瘤包括血液和实体肿瘤。一个早期有效性的试验观察以确定将来技术的整合以及发展针对其他癌症的免疫治疗策略。

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