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嵌合抗原受体:开启抗癌治疗的新时代。

Chimeric antigen receptors: unleashing a new age of anti-cancer therapy.

作者信息

Leyfman Yan

机构信息

Penn State College of Medicine, 61A University Manor East, Hershey, PA USA.

出版信息

Cancer Cell Int. 2018 Nov 14;18:182. doi: 10.1186/s12935-018-0685-x. eCollection 2018.

Abstract

BACKGROUND

Chimeric antigen receptors (CARs) represent a novel facet of modern day synthetic biology that exemplifies personalized medicine at work through their ability to harness and redirect a patient's immune system to fight cancer.

BODY

By combining the target-specificity of antibodies to the effector capabilities of T cells, CARs have yielded high remission rates for many late staged and relapsed/refractory (r/r) hematological malignancies, including acute lymphoblastic leukemias (ALL) and Non-Hodgkin's lymphomas. Despite toxicities of cytokine release syndrome and neurotoxicity, recent studies have uncovered their underlying mechanisms and devised effective therapies to manage and possibly prevent them. In 2017, CAR T cell therapy became a reality for the general public despite the high costs, when Novartis's Kymriah, became the first product to receive FDA approval for pediatric r/r B cell ALL with Gilead's Yescarta following several months later. Although effective in hematological malignancies, CAR response has been limited in solid tumors largely attributed to the heterogeneous and immunosuppressive tumor microenvironment along tumor defense mechanisms, such as antigenic escape.

CONCLUSION

Despite the current challenges of CAR T therapy, this technology is still in its infancy and its promise will continue to grow as scientists continue to develop novel approaches to enhance its efficacy. As its prevalence continues to increase, institutions and pharmaceuticals worldwide are investing in this technology in hopes of driving therapeutic innovation, while providing greater access to their respective populations through clinical trials.

摘要

背景

嵌合抗原受体(CAR)代表了现代合成生物学的一个新方面,通过利用和重定向患者的免疫系统来对抗癌症,体现了个性化医疗的作用。

正文

通过将抗体的靶向特异性与T细胞的效应能力相结合,CAR已在许多晚期和复发/难治性(r/r)血液系统恶性肿瘤中取得了高缓解率,包括急性淋巴细胞白血病(ALL)和非霍奇金淋巴瘤。尽管存在细胞因子释放综合征和神经毒性等毒性,但最近的研究已经揭示了其潜在机制,并设计出有效的治疗方法来管理甚至预防这些毒性。2017年,尽管成本高昂,但当诺华公司的Kymriah成为首个获得美国食品药品监督管理局(FDA)批准用于治疗儿科r/r B细胞ALL的产品,几个月后吉利德公司的Yescarta也获批时,CAR T细胞疗法成为了大众可及的现实。尽管CAR在血液系统恶性肿瘤中有效,但在实体瘤中的反应有限,这主要归因于肿瘤微环境的异质性和免疫抑制以及肿瘤防御机制,如抗原逃逸。

结论

尽管CAR T疗法目前面临挑战,但这项技术仍处于起步阶段,随着科学家不断开发新方法来提高其疗效,其前景将不断拓展。随着其普及程度不断提高,全球的机构和制药公司都在投资这项技术,希望推动治疗创新,同时通过临床试验让更多人能够使用该疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/897d/6236896/7491ac7d4162/12935_2018_685_Fig1_HTML.jpg

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