A Genetic Vaccine Encoding Chimeric NY-ESO-1 Induces Anticancer Immunity in A Mouse Model

Abstract: The NY-ESO-1 is one of the most immunogenic tumor antigens and an attractive candidate for developing cancer immunotherapy. However， trials using NY-ESO-1 peptide and protein vaccines so far have generated insufficient clinical outcomes， and improvement in antigen design is therefore needed for efficient cancer immunotherapy. In this study we designed different genetic vaccines (plasmids) encoding NY-ESO-1 fusion with various proteins that affect antigen processing， trafficking or presentation with the aim to identify an improved genetic adjuvant for this antigen. We studied the vaccines in a mouse model and measured humoral and cellular immune responses. We found that plasmids encoding NY-ESO-1 alone or linked with HSP70 induced strong NYESO-1-specific IgG1 response. Mice immunized with plasmid encoding ubiquitin-linked NY-ESO-1， however，induced primarily a NY-ESO-1-specific IgG2a response indicating that this genetic adjuvant drives the immune system towards a strong Th1 response. Mice immunized with plasmid encoding ubiquitin-linked NY-ESO-1 showed significant enhanced protection against challenge with a B16F10 melanoma cell line expressing NY-ESO-1 as compared to other chimeric NY-ESO-1 vaccine constructs. It demonstrated the importance of a strong Th1 response in tumor protection. Depletion of regulatory T (Treg) cells by denileukin diftitox further enhanced the antitumor effect of the ubiquitin-linked NY-ESO-1 DNA vaccine in a therapeutic study. Finally， combining ubiquitin-linked NYESO-1 construct with plasmids encoding the melanoma antigens gp100 and TRP-2 induced a synergic antitumor effect against NY-ESO-1 expressing B16F10 tumor. Overall， these data suggested that genetic vaccine encoding the ubiquitin-linked NY-ESO-1， alone or in combination with other relevant melanoma antigens might be a potent therapeutic cancer vaccine.

CSTR: 32200.14.cjcb.2015.11.0006