Immunological evaluation of full-length NY-ESO-1 protein vaccine fused to Ubiquitin against melanoma in a murine model.

Abstract

Immunological evaluation of full-length NY-ESO-1 protein vaccine fused to Ubiquitin against melanoma in a murine model.The different types of existing cancer are responsible for more than 7 million deaths per year. This way, the search for a therapeutic vaccine against cancer is increasing.Different vaccines types have been tested. Some vaccines use DNA, peptides or full-length protein as antigen for each specific type of cancer. However, other groups are investing in the production of vaccines using as antigen the DNA, peptides or full-length proteins of members belonging to cancer-testis family, since the expression of these genes is limited only germ cells of testes/ or ovaries of normal individuals, and also tumor cells from patients with different cancer types. Thus, a single vaccine can be used not only to treat a single specific type of cancer, but be extended to the treatment of a broader range of tumors. One of the cancer-testis family members most targeted to produce this vaccine type has been the NY-ESO-1, for its high immunogenicity. Some vaccines containing NY-ESO-1 peptides (SLLMWITQCFL157-167, SLLMWITQC157-165, QLSLLMWIT155-163 e LMWITQCFL159 -167) showed stabilization of disease and regression of metastases in some patients. However, these vaccines have restricted the targeted patient population by the HLA-class I type, because they promoted only CD8 + T cell response. In order to increase this immune response, other researchers used the full-length NY-ESO-1 protein as vaccine antigen, which promoted a humoral response, CD8 + and CD4+ T cell response, resulting in an enhanced immune response, since CD4 + T cells assist in the CD8 + T cell response. But formulations of this protein vaccine with some adjuvants (ISCOMATRIX ou CHP) present still a high cost for their production.In view of this, using a murine model challenged with B16 melanoma expressing NY-ESO-1 (B16-NY-ESO-1+), our project aims to evaluate the therapeutic and prophylactic potential of a vaccine cheaper and which further can be used to combat different cancer types. This new vaccine strategy consists in using as antigen the full-length NY-ESO-1 protein (that will provide both CD4+ and CD8+ T cell response) fused to a ubiquitin molecule in order to direct the antigen to be polyubiquitinated, degraded by proteasome and presented to cell surface via MHC-class I, culminating in a immune response against tumor cells mediated by NY-ESO-1-specific CD8 + T cells.