Chimeric Antigen Receptors T Cell Therapy in Solid Tumor: Challenges and Clinical Applications.
Chimeric Antigen Receptors T Cell Therapy in Solid Tumor: Challenges and Clinical Applications.
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DOI：
10.3389/fimmu.2017.01850
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发表时间：
2017
影响因子：
7.3
通讯作者：
Badie B
中科院分区：
文献类型：
--
作者：
Mirzaei HR;Rodriguez A;Shepphird J;Brown CE;Badie B
采用表达嵌合抗原受体（汽车）的工程化T淋巴细胞的连续性细胞免疫疗法（ACT）已在晚期血液癌症（如复发性或难治性急性淋巴细胞白血病、慢性淋巴细胞白血病和非霍奇金淋巴瘤）中显示出有希望的抗肿瘤作用，支持ACT向非血液恶性肿瘤的转化。尽管CAR T细胞疗法在治疗某些血液癌症患者方面取得了显著进展，但在实体瘤中的成功可能受到限制，这可能是由于异质性抗原表达、肿瘤微环境中的免疫抑制网络限制了CAR T细胞功能和持久性以及向实体瘤的次优运输。在这里，我们概述了在肿瘤微环境背景下克服CAR T细胞有效性障碍的具体方法，并提供了我们对如何扩大CAR T细胞在实体瘤中的使用可能需要修改CAR T细胞设计的观点。我们预计这些修改将进一步扩大临床实践中的CAR T细胞疗法。
Adoptive cellular immunotherapy (ACT) employing engineered T lymphocytes expressing chimeric antigen receptors (CARs) has demonstrated promising antitumor effects in advanced hematologic cancers, such as relapsed or refractory acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma, supporting the translation of ACT to non-hematological malignancies. Although CAR T cell therapy has made remarkable strides in the treatment of patients with certain hematological cancers, in solid tumors success has been limited likely due to heterogeneous antigen expression, immunosuppressive networks in the tumor microenvironment limiting CAR T cell function and persistence, and suboptimal trafficking to solid tumors. Here, we outline specific approaches to overcome barriers to CAR T cell effectiveness in the context of the tumor microenvironment and offer our perspective on how expanding the use of CAR T cells in solid tumors may require modifications in CAR T cell design. We anticipate these modifications will further expand CAR T cell therapy in clinical practice.
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