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针对新抗原的个性化癌症免疫疗法的免疫药物基因组学

Immunopharmacogenomics towards personalized cancer immunotherapy targeting neoantigens.

作者信息

Kiyotani Kazuma, Chan Hiu Ting, Nakamura Yusuke

机构信息

Project for Immunogenomics, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan.

Department of Medicine, The University of Chicago, Chicago, IL, USA.

出版信息

Cancer Sci. 2018 Mar;109(3):542-549. doi: 10.1111/cas.13498. Epub 2018 Feb 14.

Abstract

Utilizing the host immune system to eradicate cancer cells has been the most investigated subject in the cancer research field in recent years. However, most of the studies have focused on highly variable responses from immunotherapies such as immune checkpoint inhibitors, from which the majority of patients experienced no or minimum clinical benefit. Advances in genomic sequencing technologies have improved our understanding of immunopharmacogenomics and allowed us to identify novel cancer-specific immune targets. Highly tumor-specific antigens, neoantigens, are generated by somatic mutations that are not present in normal cells. It is plausible that by targeting antigens with high tumor-specificity, such as neoantigens, the likelihood of toxic effects is very limited. However, understanding the interaction between neoantigens and the host immune system remains a significant challenge. This review focuses on the potential use of neoantigen-targeted immunotherapies in cancer treatment and the recent progress of different strategies in predicting, identifying, and validating neoantigens. Successful identification of highly tumor-specific antigens accelerates the development of personalized immunotherapy with no or minimum adverse effects and with a broader coverage of patients.

摘要

近年来,利用宿主免疫系统根除癌细胞一直是癌症研究领域中研究最多的课题。然而,大多数研究都集中在免疫疗法(如免疫检查点抑制剂)的高度可变反应上,大多数患者从中没有获得或仅获得最小的临床益处。基因组测序技术的进步增进了我们对免疫药物基因组学的理解,并使我们能够识别新的癌症特异性免疫靶点。高度肿瘤特异性抗原,即新抗原,是由正常细胞中不存在的体细胞突变产生的。通过靶向具有高肿瘤特异性的抗原(如新抗原),产生毒性作用的可能性非常有限,这似乎是合理的。然而,了解新抗原与宿主免疫系统之间的相互作用仍然是一项重大挑战。本综述重点关注新抗原靶向免疫疗法在癌症治疗中的潜在应用以及预测、识别和验证新抗原的不同策略的最新进展。成功识别高度肿瘤特异性抗原可加速无或最小副作用且覆盖更广泛患者群体的个性化免疫疗法的开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bb9/5834780/d7dfbc83f504/CAS-109-542-g001.jpg

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