Microencapsulation of tumor lysates and live cell engineering with MIP-3α as an effective vaccine.

ABSTRACT

The combination of several potential strategies so as to develop new tumor vaccines is an attractive field of translational medicine. Pulsing tumor lysates with dendritic cells (DCs), in-vivo attraction of DCs by macrophage inflammatory protein 3α (MIP-3α), and reversion of the tumor suppressive microenvironment have been tested as strategies to develop tumor vaccines. In this study, we generated an alginate microsphere (named PaLtTcAdMIP3α) that encapsulated tumor lysates, live tumor cells engineering with a recombinant MIP-3α adenovirus and BCG. We used PaLtTcAdMIP3α as a model vaccine to test its antitumor activities. Our results showed that PaLtTcAdMIP3α expressed and excreted MIP-3α, which effectively attracted DCs ex vivo and in vivo. Injection of PaLtTcAdMIP3α into tumor-bearing mice effectively induced both therapeutic and prophylactic antitumor immunities in CT26, Meth A, B16-F10 and H22 models, but without any ensuing increase in adverse effects. Both tumor-specific cellular and humoral immune responses, especially the CD8(+) T cell-dependent cytotoxic T immunity, were found in the mice injected with PaLtTcAdMIP3α. The anti-tumor activity was abrogated completely by depletion of CD8(+) and partially by CD4(+) T lymphocytes. In addition, the number of IFN-γ-producing CD8(+) T cells in spleen and tumor tissues was significantly increased; but the number of CD4(+)CD25(+)FOXP3(+) regulatory T cells (Treg) in tumor tissues was decreased. These data strongly suggest that a combination of multi-current-using strategies such as the novel approach of using our PaLtTcAdMIP3α microspheres could be an effective tumor model vaccine.