个性化肿瘤新抗原疫苗中抗原肽预测研究进展

失控的突变导致肿瘤的发生,其中某些非同义突变(错义、移码、融合)多肽,被蛋白酶体降解成短肽后被抗原提呈细胞(antigen-presenting cells,APCs)识别,呈递至引流淋巴结,符合主要组织相容性复合物(major histocompatibility complex,MHC)结合基序的短肽,继而被T细胞表面因子捕获而产生免疫反应,引发肿瘤的消退,我们称之为"新抗原"(neoantigens).这类抗原由于未受胸腺的阴性筛选,被T细胞识别为"异类",不易受免疫耐受机制的影响,从而可作为免疫介导肿瘤治疗的有效靶点.新一代测序技术极大推动了新抗原疫苗的可行性,但从测序识别肿瘤的体细胞突变到TCR (Tcell receptor)识别新抗原产生免疫反应,中间存在着大量的候选假阳性新抗原多肽,这对于针对新抗原而设计疫苗无疑是难以跨越的障碍.一套有效合理的筛选方法,是新抗原疫苗制备过程中不可或缺的一环.然而国内未见相关综述报道,本文调研了目前新抗原免疫治疗过程中的新抗原肽预测及筛选研究进展.

Advances in The Prediction of Antigenic Peptides in Personalized Tumor Neoantigen Vaccine

Runaway mutations cause tumors, some of the non-synonymous mutational (i.e., missense, frameshift, fusion) peptides are degraded into short peptides by proteasome, then APCs (antigen-presenting cells) recognize and present them to draining lymph nodes. These short peptides, in line with the combination of MHC (major histocompatibility complex) motif, are captured by the T cell surface factors and produce an immune response, eventually lead to tumor regression. We call these peptides neoantigens, because these antigens are not negatively screened by thymus gland, they are recognized as "alien" by T cells and are not susceptible to immune tolerance mechanism. Neoantigens can act as effective targets for immune-mediated tumor control. The next generation sequencing technology greatly boosts the feasibility of neoantigen vaccine design, however identifying tumor somatic mutations that can be presented and recognized by TCR (T-cell receptor) is a very demanding yet key step. Many of the predicted "positive" neoantigen peptides are actually "false" and need to be eliminated in further steps to clinical application. Therefore effective screening method is an indispensable part of neoantigen vaccine therapy. However, no related reports have been seen in domestic. In this paper, the computational prediction process of screening methods for potential neoantigen peptides are reviewed.