In this communication, we will analyze some important factors and immunological phenomena related to neoantigen cancer vaccines, with particular emphasis on recently published Phase I clinical trials. Several obstacles and issues are addressed that challenge the current paradigm and inquire if neoantigens, which are essentially single-use vaccine candidates, are legitimate targets to induce protective immune responses with regard to the evolving mutational landscape. We also share insights into the striking similarities between cancer and antigenically variable pathogens and suggest that any successful vaccine against either should demonstrate a similar property: efficient induction of a diverse pool of immune cells equipped to prevent immune escape. Hence, to confront antigenic variability directly, we have employed our innovative vaccine concept, Variable Epitope Libraries, composed of large combinatorial libraries of heavily mutated epitopes, as a “universal” vaccine platform. Collectively, we offer critical analyses on key issues, which ultimately reflect on the prospective clinical relevance of personalized neoantigen vaccines which is still undefined.

在本次交流中，我们将分析与新抗原癌症疫苗相关的一些重要因素和免疫学现象，特别强调最近发表的 I 期临床试验。解决了一些挑战当前范式的障碍和问题，并询问新抗原（基本上是一次性疫苗候选者）是否是针对不断变化的突变环境诱导保护性免疫反应的合法目标。我们还分享了对癌症和抗原可变病原体之间惊人相似之处的见解，并建议任何针对两者的成功疫苗都应表现出类似的特性：有效诱导多样化的免疫细胞池，以防止免疫逃逸。因此，为了直接对抗抗原变异，我们采用了创新的疫苗概念，可变表位文库，由重度突变表位的大型组合文库组成，作为“通用”疫苗平台。总的来说，我们对关键问题进行了批判性分析，最终反映了个性化新抗原疫苗的前瞻性临床相关性，但目前仍未明确。