Makita Shinichi, Yoshimura Kiyoshi, Tobinai Kensei
Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
Department of Experimental Therapeutics and Exploratory Oncology Research and Clinical Trial Center, National Cancer Center Hospital, Tokyo, Japan.
Cancer Sci. 2017 Jun;108(6):1109-1118. doi: 10.1111/cas.13239. Epub 2017 May 25.
B-cell non-Hodgkin lymphoma (B-NHL) is the most frequent hematological malignancy. Although refined chemotherapy regimens and several new therapeutics including rituximab, a chimeric anti-CD20 monoclonal antibody, have improved its prognosis in recent decades, there are still a substantial number of patients with chemorefractory B-NHL. Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is expected to be an effective adoptive cell treatment and has the potential to overcome the chemorefractoriness of B-cell leukemia and lymphoma. Recently, several clinical trials have shown remarkable efficacy of anti-CD19 CAR T-cell therapy, not only in B-acute lymphoblastic leukemia but also in B-NHL. Nonetheless, there are several challenges to overcome before introduction into clinical practice, such as: (i) further refinement of the manufacturing process, (ii) further improvement of efficacy, (iii) finding the optimal infusion cell dose, (iv) optimization of lymphocyte-depleting chemotherapy, (v) identification of the best CAR structure, and (vi) optimization of toxicity management including cytokine release syndrome, neurologic toxicity, and on-target off-tumor toxicity. Several ways to solve these problems are currently under study. In this review, we describe the updated clinical data regarding anti-CD19 CAR T-cell therapy, with a focus on B-NHL, and discuss the clinical implications and perspectives of CAR T-cell therapy.
B细胞非霍奇金淋巴瘤（B-NHL）是最常见的血液系统恶性肿瘤。尽管近几十年来，优化的化疗方案以及包括嵌合抗CD20单克隆抗体利妥昔单抗在内的几种新疗法改善了其预后，但仍有相当数量的化疗难治性B-NHL患者。抗CD19嵌合抗原受体（CAR）T细胞疗法有望成为一种有效的过继性细胞治疗方法，并且有潜力克服B细胞白血病和淋巴瘤的化疗难治性。最近，多项临床试验表明抗CD19 CAR T细胞疗法不仅对B急性淋巴细胞白血病有效，对B-NHL也有显著疗效。尽管如此，在引入临床实践之前仍有几个挑战需要克服，例如：（i）进一步优化生产工艺；（ii）进一步提高疗效；（iii）确定最佳的输注细胞剂量；（iv）优化淋巴细胞清除化疗；（v）确定最佳的CAR结构；（vi）优化毒性管理，包括细胞因子释放综合征、神经毒性和靶向脱肿瘤毒性。目前正在研究解决这些问题的几种方法。在本综述中，我们描述了关于抗CD19 CAR T细胞疗法的最新临床数据，重点是B-NHL，并讨论了CAR T细胞疗法的临床意义和前景。
