CART Immunotherapy: Development, Success, and Translation to Malignant Gliomas and Other Solid Tumors.
CART Immunotherapy: Development, Success, and Translation to Malignant Gliomas and Other Solid Tumors.
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DOI：
10.3389/fonc.2018.00453
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发表时间：
2018
影响因子：
4.7
通讯作者：
Dey M
中科院分区：
文献类型：
--
作者：
Filley AC;Henriquez M;Dey M
T细胞嵌合抗原受体（CAR）技术允许将高度的肿瘤选择性引入过继性细胞转移疗法。这项技术的发展产生了一种强大的抗肿瘤免疫策略，在液体癌中取得了显著的效果。靶向CD19和CD20的CAR表达T细胞（CART）已成功用于治疗血液恶性肿瘤，在大多数治疗患者中产生持续的肿瘤消退。这些令人鼓舞的结果导致FDA历史性地批准了CTL 019，诺华的CAR T细胞疗法用于治疗复发性或难治性B细胞急性淋巴细胞白血病（ALL）的儿童和年轻人。然而，将该技术转化为实体瘤，如恶性神经胶质瘤（MG），迄今为止尚未成功。这篇综述及时分析了导致CART免疫治疗在血液恶性肿瘤中成功的因素，限制其在实体瘤治疗中成功的障碍，以及克服这些挑战的方法，并允许将CART免疫治疗应用于迫切需要有效治疗的难治性肿瘤（如恶性胶质瘤）的治疗方式。
T cell chimeric antigen receptor (CAR) technology has allowed for the introduction of a high degree of tumor selectivity into adoptive cell transfer therapies. Evolution of this technology has produced a robust antitumor immunotherapeutic strategy that has resulted in dramatic outcomes in liquid cancers. CAR-expressing T-cells (CARTs) targeting CD19 and CD20 have been successfully used in the treatment of hematologic malignancies, producing sustained tumor regressions in a majority of treated patients. These encouraging results have led to a historic and unprecedented FDA approval of CTL019, Novartis' CAR T-cell therapy for the treatment of children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). However, the translation of this technology to solid tumors, like malignant gliomas (MG), has thus far been unsuccessful. This review provides a timely analysis of the factors leading to the success of CART immunotherapy in the setting of hematologic malignancies, barriers limiting its success in the treatment of solid tumors, and approaches to overcome these challenges and allow the application of CART immunotherapy as a treatment modality for refractory tumors, like malignant gliomas, that are in desperate need of effective therapies.
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