Generation of multiepitope cancer vaccines based on large combinatorial libraries of survivin-derived mutant epitopes.

Generation of multiepitope cancer vaccines based on large combinatorial libraries of survivin-derived mutant epitopes. Immunology. 2020 Jul 03;: Authors: Domínguez-Romero AN, Martínez-Cortés F, Munguía ME, Odales J, Gevorkian G, Manoutcharian K Abstract Immune tolerance is the main challenge in the field of cancer vaccines, therefore, modified peptide sequences or naturally occurring mutated versions of cancer-related wild-type (WT) antigens represent a promising pathway. However, low immunogenicity of mutation-induced neoantigens and, particularly, their incapacity to activate CD8+ T cells are generating doubts on the success of neoantigen-based cancer vaccines in clinical trials. We developed a novel vaccine approach based on a new class of vaccine immunogens, called Variable Epitope Libraries (VELs). We used 3 regions of survivin (SVN), composed of 40, 49 and 51 amino acids, along with the complete SVN protein to generate the VELs as multi-epitope vaccines. BALB/c mice, challenged with the aggressive and highly metastatic 4T1 cell line, were vaccinated in therapeutic setting. We showed significant tumor growth inhibition and, most importantly, strong suppression of lung metastasis after a single immunization utilizing VEL vaccines. We demonstrated vaccine-induced broad cellular immune responses concomitant with extensive tumor infiltration of T cells, the activation of CD107a+IFN-γ+ T cells in the spleen and a significant inc...
Source: Immunology - Category: Allergy & Immunology Authors: Tags: Immunology Source Type: research