Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), AP 70228, Ciudad Universitaria, 04510, Mexico, DF, Mexico.
Arch Immunol Ther Exp (Warsz). 2021 Apr 28;69(1):12. doi: 10.1007/s00005-021-00615-8.
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.
在本通讯中，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，特别关注最近发表的 I 期临床试验。我们还探讨了一些挑战当前范式的障碍和问题，并探讨了新抗原（本质上是一次性使用的疫苗候选物）是否是诱导针对不断变化的突变景观的保护性免疫反应的合理靶标。我们还分享了对癌症和抗原可变病原体之间惊人相似性的见解，并提出任何针对这两者的成功疫苗都应该表现出类似的特性：有效诱导大量免疫细胞，以防止免疫逃逸。因此，为了直接应对抗原变异性，我们采用了我们的创新疫苗概念——可变表位文库，该文库由大量重突变表位的组合文库组成，作为一种“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，这些问题最终反映了个性化新抗原疫苗的预期临床相关性，而这一点仍然尚未确定。
