CAR T-cell therapy for lung cancer and malignant pleural mesothelioma.

CAR T-cell therapy for lung cancer and malignant pleural mesothelioma.
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DOI:
10.1016/j.trsl.2017.04.004
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发表时间:
2017-09
期刊:
Translational research : the journal of laboratory and clinical medicine
影响因子:
--
通讯作者:
Adusumilli PS
Adusumilli PS
中科院分区:
其他
文献类型:
--
作者:
Zeltsman M;Dozier J;McGee E;Ngai D;Adusumilli PS

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免疫疗法是一个很有前途的领域,它利用免疫系统的力量作为癌症治疗的治疗剂。在具有相对较高的肿瘤浸润性T细胞的非小细胞肺癌(NSCLC)和恶性胸膜间皮瘤(MPM)患者中显示的有益结果,结合在NSCLC患者队列中在检查点阻断治疗后获得的令人印象深刻的应答,为促进这些患者的效应免疫应答奠定了坚实的基础。正在研究的一种这样的方法是施用肿瘤抗原靶向的T细胞并转导嵌合抗原受体(CAR)。汽车是增强T细胞抗肿瘤效应子功能的合成受体,并且基于最近治疗B细胞恶性血液病患者的临床试验的成功,已经获得了在实体瘤中研究的动力。本文综述了在临床前研究以及NSCLC和MPM患者的临床试验中正在研究的CAR T细胞治疗的靶抗原。我们讨论了NSCLC和MPM患者联合免疫治疗的基本原理。此外,我们还强调了克服CAR T细胞疗法转化为实体瘤所面临的障碍的挑战和策略。
Immunotherapy is a promising field that harnesses the power of the immune system as a therapeutic agent for cancer treatment. Beneficial outcomes shown in patients with non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM) with relatively higher tumor-infiltrating T cells, combined with impressive responses obtained in a cohort of patients with NSCLC following checkpoint blockade therapy, lays a strong foundation to promote effector immune responses in these patients. One such approach being investigated is administration of tumor antigen-targeted T cells with transduction of a chimeric antigen receptor (CAR). CARs are synthetic receptors that enhance T-cell antitumor effector function and have gained momentum to investigate in solid tumors based on recent successes of clinical trials treating patients with B-cell hematologic malignancies. This review summarizes target antigens for CAR T-cell therapy that are being investigated in preclinical studies as well as clinical trials for both NSCLC and MPM patients., We discuss the rationale for combination immunotherapies for NSCLC and MPM patients. Additionally, we have highlighted the challenges and strategies for overcoming the obstacles facing translation of CAR T-cell therapy to solid tumors.
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