PDF(Pubmed)
Abstract：
Neoantigens, presented as peptides on the surfaces of cancer cells, have recently been proposed as optimal targets for immunotherapy in clinical practice. The promising outcomes of neoantigen-based cancer vaccines have inspired enthusiasm for their broader clinical applications. However, the individualized tumor-specific antigens (TSA) entail considerable costs and time due to the variable immunogenicity and response rates of these neoantigens-based vaccines, influenced by factors such as neoantigen response, vaccine types, and combination therapy. Given the crucial role of neoantigen efficacy, a number of bioinformatics algorithms and pipelines have been developed to improve the accuracy rate of prediction through considering a series of factors involving in HLA-peptide-TCR complex formation, including peptide presentation, HLA-peptide affinity, and TCR recognition. On the other hand, shared neoantigens, originating from driver mutations at hot mutation spots (e.g., KRASG12D), offer a promising and ideal target for the development of therapeutic cancer vaccines. A series of clinical practices have established the efficacy of these vaccines in patients with distinct HLA haplotypes. Moreover, increasing evidence demonstrated that a combination of tumor associated antigens (TAAs) and neoantigens can also improve the prognosis, thus expand the repertoire of shared neoantigens for cancer vaccines. In this review, we provide an overview of the complex process involved in identifying personalized neoantigens, their clinical applications, advances in vaccine technology, and explore the therapeutic potential of shared neoantigen strategies.
摘要：
新抗原，呈现为癌细胞表面的肽，最近被提出作为临床实践中免疫疗法的最佳靶标。基于新抗原的癌症疫苗的有希望的结果激发了他们更广泛的临床应用的热情。然而,由于这些基于新抗原的疫苗的不同免疫原性和应答率，个体化肿瘤特异性抗原(TSA)需要相当大的成本和时间。受到新抗原反应等因素的影响，疫苗类型，和联合治疗。鉴于新抗原功效的关键作用，通过考虑一系列涉及HLA-肽-TCR复合物形成的因素，已经开发了许多生物信息学算法和管道来提高预测的准确率，包括肽呈递，HLA-肽亲和力，和TCR识别。另一方面,共有的新抗原，源自热点突变点的驱动突变(例如，KRASG12D),为开发治疗性癌症疫苗提供了一个有希望和理想的目标。一系列临床实践已经确立了这些疫苗在具有不同HLA单倍型的患者中的功效。此外，越来越多的证据表明，肿瘤相关抗原（TAA）和新抗原的组合也可以改善预后，从而扩大了癌症疫苗共享新抗原的库。在这次审查中,我们概述了识别个性化新抗原所涉及的复杂过程，它们的临床应用，疫苗技术的进步，并探索共享新抗原策略的治疗潜力。
