Cancer neoantigens as potential targets for immunotherapy.
Cancer neoantigens as potential targets for immunotherapy.
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DOI：
10.1007/s10585-021-10091-1
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发表时间：
2022-03
影响因子：
4
通讯作者：
Li T
中科院分区：
文献类型：
--
作者：
Ma W;Pham B;Li T
针对细胞毒性t淋巴细胞相关蛋白-4 （CTLA-4）和程序性细胞死亡蛋白1 （PD-1）或其配体PD-L1的免疫检查点抑制剂（ICIs）已经提高了各种疾病情况下许多癌症类型患者的生存率和治愈率。然而，只有10-40%的癌症患者受益于这些ici，其中约20%的患者由于严重甚至致命的免疫相关不良事件而中断或停止治疗。目前，精准免疫治疗的工作主要集中在改善基于生物标志物的现有ici患者选择，探索基本原理组合和新策略，以扩大免疫治疗对更多癌症患者的益处。新抗原产生于癌细胞中约10%的非同义体细胞突变，是个体患者T细胞介导的抗肿瘤免疫的重要靶点。下一代测序技术和计算生物信息学的进步使个体肿瘤的基因组改变、推定的新抗原和基因表达谱的识别能够以一种快速和经济的方式用于个人肿瘤学。在基因组生物标志物中，有缺陷的错配DNA修复（dMMR）、微卫星不稳定性高（MSI-H）和高肿瘤突变负担（H-TMB）已获得FDA批准，可用于选择ICI治疗的患者。所有这些生物标志物测量高新抗原负荷和肿瘤抗原性，支持当前针对高TMB肿瘤患者的基于新抗原的个性化癌症疫苗的开发。几项研究表明，新抗原疫苗在转移性和佐剂性高TMB肿瘤患者中是可行、安全的，并且具有良好的临床活性。本文综述了基于新抗原的个体化免疫治疗的最新数据和技术。
Immune checkpoint inhibitors (ICIs) targeting the cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and programed cell death protein 1 (PD-1) or its ligand PD-L1 have increased the survival and cure rates for patients with many cancer types in various disease settings. However, only 10–40% of cancer patients benefited from these ICIs, of whom ~ 20% have treatment interruption or discontinuation due to immune-related adverse events that can be severe and even fatal. Current efforts in precision immunotherapy are focused on improving biomarker-based patient selection for currently available ICIs and exploring rationale combination and novel strategies to expand the benefit of immunotherapy to more cancer patients. Neoantigens arise from ~ 10% of the non-synonymous somatic mutations in cancer cells, are important targets of T cell-mediated anti-tumor immunity for individual patients. Advances in next generation sequencing technology and computational bioinformatics have enable the identification of genomic alterations, putative neoantigens, and gene expression profiling in individual tumors for personal oncology in a rapid and cost-effective way. Among the genomic biomarkers, defective mismatch DNA repair (dMMR), microsatellite instability high (MSI-H) and high tumor mutational burden (H-TMB) have received FDA approvals for selecting patients for ICI treatment. All these biomarkers measure high neoantigen load and tumor antigenicity, supporting the current development of neoantigen-based personalized cancer vaccines for patients with high TMB tumor. Several studies have shown neoantigen vaccines are feasible, safe and have promising clinical activity in patients with high TMB tumors in both metastatic and adjuvant settings. This review summarizes the emerging data and technologies for neoantigen-based personalized immunotherapy.
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影响因子：
82.9
作者：
AbdulJabbar K;Raza SEA;Rosenthal R;Jamal-Hanjani M;Veeriah S;Akarca A;Lund T;Moore DA;Salgado R;Al Bakir M;Zapata L;Hiley CT;Officer L;Sereno M;Smith CR;Loi S;Hackshaw A;Marafioti T;Quezada SA;McGranahan N;Le Quesne J;TRACERx Consortium;Swanton C;Yuan Y
通讯作者：
Yuan Y
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影响因子：
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作者：
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Kakimi K
影响因子：
12.3
作者：
Goodman, Aaron M.;Castro, Andrea;Kurzrock, Razelle
通讯作者：
Kurzrock, Razelle
影响因子：
10.3
作者：
Bareche, Yacine;Buisseret, Laurence;Sotiriou, Christos
通讯作者：
Sotiriou, Christos
IV期或复发性非小细胞肺癌中的一线Nivolumab。
DOI：
10.1056/nejmoa1613493
发表时间：
2017-06-22
期刊：
The New England journal of medicine
影响因子：
--
作者：
Carbone DP;Reck M;Paz-Ares L;Creelan B;Horn L;Steins M;Felip E;van den Heuvel MM;Ciuleanu TE;Badin F;Ready N;Hiltermann TJN;Nair S;Juergens R;Peters S;Minenza E;Wrangle JM;Rodriguez-Abreu D;Borghaei H;Blumenschein GR Jr;Villaruz LC;Havel L;Krejci J;Corral Jaime J;Chang H;Geese WJ;Bhagavatheeswaran P;Chen AC;Socinski MA;CheckMate 026 Investigators
通讯作者：
CheckMate 026 Investigators