ESAT-6-gpi DNA vaccine augmented the specific antitumour efficacy induced by the tumour vaccine B16F10-ESAT-6-gpi/IL-21 in a mouse model

Abstract

In this study, we hypothesized that the mice immunized with the glycosylphosphatidylinositol (GPI) anchored 6-kDa early-secreted antigenic target (ESAT-6) DNA vaccine (ESAT-6-gpi) and the tumour vaccine B16F10-ESAT-6-gpi/IL-21 might significantly enhance immune responses and antimelanoma efficacy. Our experimental results indicated that the anti-ESAT-6 antibody induced by the DNA vaccine ESAT-6-gpi bound ESAT-6 to the surface of tumour vaccine to activate a complement classical pathway and resulted in the B16F10 tumour cell lysis and apoptosis, which served as a potential trigger for breaking melanomatous immune tolerance to elicit an initiation of natural antimelanoma immunity. Our innovative approach of using the DNA vaccine ESAT-6-gpi priming and the tumour vaccine B16F10-ESAT-6-gpi/IL-21 boosting induced strong antimelanoma immunity that inhibited melanomatous growth. These findings highlighted the DNA vaccine ESAT-6-gpi as an immune enhancer to augment the immune efficacy of the tumour vaccine B16F10-ESAT -6-gpi/IL-21 against melanoma in a mouse model.