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恶性神经胶质瘤免疫治疗的新希望:过继性 T 细胞转移治疗。

A new hope in immunotherapy for malignant gliomas: adoptive T cell transfer therapy.

机构信息

Department of Neurosurgery, Incheon St. Mary's Hospital, The Catholic University of Korea College of Medicine, Dongsuro 56, Bupyeong-gu, Incheon 403-720, Republic of Korea.

Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Banpodaero 222, Seocho-gu, Seoul 137-701, Republic of Korea.

出版信息

J Immunol Res. 2014;2014:326545. doi: 10.1155/2014/326545. Epub 2014 Jun 9.

Abstract

Immunotherapy emerged as a promising therapeutic approach to highly incurable malignant gliomas due to tumor-specific cytotoxicity, minimal side effect, and a durable antitumor effect by memory T cells. But, antitumor activities of endogenously activated T cells induced by immunotherapy such as vaccination are not sufficient to control tumors because tumor-specific antigens may be self-antigens and tumors have immune evasion mechanisms to avoid immune surveillance system of host. Although recent clinical results from vaccine strategy for malignant gliomas are encouraging, these trials have some limitations, particularly their failure to expand tumor antigen-specific T cells reproducibly and effectively. An alternative strategy to overcome these limitations is adoptive T cell transfer therapy, in which tumor-specific T cells are expanded ex vivo rapidly and then transferred to patients. Moreover, enhanced biologic functions of T cells generated by genetic engineering and modified immunosuppressive microenvironment of host by homeostatic T cell expansion and/or elimination of immunosuppressive cells and molecules can induce more potent antitumor T cell responses and make this strategy hold promise in promoting a patient response for malignant glioma treatment. Here we will review the past and current progresses and discuss a new hope in adoptive T cell therapy for malignant gliomas.

摘要

免疫疗法作为一种有前途的治疗方法,针对高度难治性恶性脑胶质瘤,具有肿瘤特异性细胞毒性、最小的副作用和记忆 T 细胞的持久抗肿瘤作用。但是,免疫疗法(如疫苗接种)诱导的内源性激活 T 细胞的抗肿瘤活性不足以控制肿瘤,因为肿瘤特异性抗原可能是自身抗原,肿瘤具有免疫逃逸机制来逃避宿主的免疫监视系统。尽管恶性脑胶质瘤疫苗策略的最近临床结果令人鼓舞,但这些试验存在一些局限性,特别是它们未能有效地、可重复地扩增肿瘤抗原特异性 T 细胞。克服这些局限性的另一种策略是过继性 T 细胞转移疗法,其中肿瘤特异性 T 细胞在体外快速扩增,然后转移给患者。此外,通过遗传工程增强 T 细胞的生物学功能,通过同种型 T 细胞扩增和/或消除免疫抑制细胞和分子来修饰宿主的免疫抑制微环境,可以诱导更有效的抗肿瘤 T 细胞反应,使这种策略有望促进患者对恶性脑胶质瘤治疗的反应。在这里,我们将回顾过去和现在的进展,并讨论过继性 T 细胞治疗恶性脑胶质瘤的新希望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/287b/4070364/fa94e466dc74/JIR2014-326545.001.jpg

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