GLMEEMSAL epitope common in different isoforms of hMena elicits in vitro activation of cytotoxic T cells and stimulates specific antitumor immunity in BALB/c mice.

BACKGROUND

Alternative expression of human ortholog of murine Mena (hMena) hMena/hMena and hMena/hMenaΔv6 isoforms regulate the invasiveness and metastatic potential of tumor cells. It is then important to identify epitopes of these proteins that can elicit antitumor immune response to contribute to the elimination of cells with metastatic potential.

METHODS

We assayed the capacity of the peptide GLMEEMSAL, common in hMena/hMena and hMena/hMenaΔv6 isoforms, to generate an antitumor immune response through an in vitro vaccination system with mature dendritic cells (MDC) loaded with this peptide and in vivo immunization using a tumor model with the mammary adenocarcinoma JC cell line to induce tumors in BALBc mice.

RESULTS

MDC loaded with the peptide GLMEEMSAL elicited strong proliferation and activation of CD8 T lymphocytes. The CTLs generated with this system were capable to lyse specifically BrCa and CeCa cell lines expressing either hMena/hMena or hMena/hMenaΔv6. Immunization with GLMEEMSAL provided protective and therapeutic antitumor activity as well as increased survival in BALB/c mice.

CONCLUSION

These results are highly relevant for the use of common peptides among the different isoforms of hMena to develop immunotherapy protocols to counteract the growth and metastatic potential of tumors with over-expression of hMena.