Immunopharmacogenomics towards personalized cancer immunotherapy targeting neoantigens

被引:41
|
作者
Kiyotani, Kazuma [1 ]
Chan, Hiu Ting [1 ]
Nakamura, Yusuke [2 ,3 ]
机构
[1] Japanese Fdn Canc Res, Project Immunogen, Canc Precis Med Ctr, Tokyo, Japan
[2] Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA
[3] Univ Chicago, Dept Surg, 5841 S Maryland Ave, Chicago, IL 60637 USA
来源
CANCER SCIENCE | 2018年 / 109卷 / 03期
关键词
cancer precision medicine; immune checkpoint inhibitor; neoantigen; next-generation sequencing; T-cell receptor repertoire; GENERATION SEQUENCING DATA; T-CELL EPITOPES; METASTATIC MELANOMA; MASS-SPECTROMETRY; PD-1; BLOCKADE; NEO-ANTIGENS; PROTEASOMAL CLEAVAGE; SOMATIC MUTATIONS; COMPLETE RESPONSE; CTLA-4;
D O I
10.1111/cas.13498
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页码:542 / 549
页数:8
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