Universal cancer peptide-based therapeutic vaccine breaks tolerance against telomerase and eradicates established tumor
Menée in vitro et à l'aide de modèles murins transgéniques, cette étude montre qu'un vaccin thérapeutique universel à base de peptides dérivés de la sous-unité TERT de la télomérase induit une réponse immunitaire antitumorale dans différents types de cancer
Purpose:To evaluate CD4+ helper functions and antitumor effect of promiscuous universal cancer peptides (UCP) derived from telomerase reverse transcriptase (TERT). Experimental Design: To evaluate the widespread immunogenicity of UCPs in human, spontaneous T cell responses against UCPs were measured in various types of cancer using T cell proliferation and ELISPOT assays. The humanized HLA-DRB1*0101/HLA-A*0201 transgenic mice was used to study CD4+ helper effects of UCPs on antitumor CTL responses. UCP-based antitumor therapeutic vaccine was evaluated using an HLA-A*0201positive B16 melanoma that express TERT. Results: Presence of high number of UCP-specific CD4+ T cells was found in the blood of patients with various types of cancer. These UCP-specific T cells mainly produce IFN-γ and TNF- . In HLA transgenic mice, UCPs vaccinations induce high avidity CD4+ Th1 cells and activated dendritic cells that produced interleukin 12. UCP-based vaccination breaks self tolerance against TERT and enhances primary and memory CTL responses. Furthermore, the use of UCP strongly improves the efficacy of therapeutic vaccination against established B16-HLA-A*0201 melanoma and promotes tumor infiltration by TERT-specific CD8+ TILs. Conclusions: Ours results showed that UCP-based vaccinations strongly stimulate antitumor immune responses and could be used to design efficient immunotherapies in multiple types of cancers.