CAR-T细胞治疗：物理屏障和免疫抑制在淋巴瘤中的作用

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CAR T-Cell Therapy: The Role of Physical Barriers and Immunosuppression in Lymphoma.

Abstract

Chimeric antigen receptor (CAR) T-cells have shown remarkable results in patients with B-cell leukemia and lymphoma. However, while CAR T-cells have shown complete responses in a majority of patients with acute lymphoblastic leukemia (ALL), lymphomas are more difficult to treat. Different CAR designs and conditioning protocols seem to affect the persistence of patient responses. However, factors that determine if patients receiving the same CARs will respond or not remain obscure. In Sweden, a phase I/IIa trial using third-generation CAR T-cells is ongoing in which we intend to compare tumor biology and immunology, in each patient, to treatment response. CAR T-cell therapy is a powerful tool to add to the treatment options for this patient group but we need to perform the necessary basic research on the multifactorial mechanisms of action to give patients the best possible option of survival. Such studies are also crucial to expand the success of CAR T-cells beyond CD19+ B-cell malignancy. This review will focus on possible barriers of treating lymphoma to define factors that need to be investigated to develop the next generation of CAR T-cell therapy.

CAR-T细胞治疗：物理屏障和免疫抑制在淋巴瘤中的作用

摘要：

CAR-T细胞治疗技术已经在B细胞白血病和淋巴瘤病人中展现了显著的治疗效果。然而，当CAR-T细胞在大多数的急性淋巴细胞白血病患者中展现了完全的有效性，但对于淋巴瘤，CAR-T技术还是存在困难。在瑞典，一个使用三代的CAR-T细胞的I期和II期试验正在进行，我们打算对比每一个病人的肿瘤生物学和免疫学，以及每个患者的治疗反应。CAR-T细胞治疗技术是一个强有力的工具，需要增加到治疗病人的观点中，然而，我们需要进行必要的基础研究，研究多因素的作用机制，给患者最好的生存选择。这个研究也很重要，对于靶向CD19的CAR-T细胞治疗B细胞淋巴瘤。这篇综述集中讨论治疗治疗淋巴瘤的可能的障碍，确定需要进行调查的因素，发展下一代的CAR-T细胞治疗。