Antitumor Effect of a Whole Tumor Cell Vaccine Expressing Human Fibroblast Activation Protein in Murine Tumor Models.

e14542 Background: Immunosuppressive factors in the tumor microenvironment reduce the therapeutic efficacy of cancer vaccines; therefore, dampening the tumor immunosuppressive environment while activating antitumor immunity should be a useful approach for cancer therapy. Cancer-associated fibroblasts (CAFs) are among the most important cellular components of the tumor microenvironment and play an important role in the development and progression of tumors. Fibroblast activation protein α (FAPα) is a type II transmembrane protein specifically expressed by CAFs in most epithelial cancers. Gene sequence homology between human and murine FAPα is 90%. Heterogeneity of genes in the evolution of the formation of such nuances can be utilized to break immune tolerance, enhance immunogenicity, induce tumour cell autoimmune responses and thus inhibit tumor growth. Methods: Tumor cells were transfected with human FAPα plasmids employing the cationic lipid DOTAP. Its antitumor effects were investigated in three established tumor models. The potential immune mechanisms were investigated through adoptive immunotherapy and 51Cr release assay. The distributions of the immune cells in the tumor microenvironment were detected by immunohistochemical staining and flow cytometry. Results: Our results shown that whole tumor cell vaccine expressing human FAPα significantly inhibit tumor growth and prolong the survival of tumor bearing mice. This antitumor immune response was involved both of cellular and humoral immune responses. FAPα specific neutralizing antibodies were found in the serum of vaccinated mice and CAFs were significantly reduced within the tumors. Furthermore, this vaccine enhanced the infiltration of CD4+ T cells and CD8+ T cells, and suppressed the accumulation of immunosuppressive cells in the tumor microenvironment. Conclusions: These findings suggest that whole tumor cell vaccine expressing human FAPα inhibit tumor growth by producing FAPα specific neutralizing antibodies and CTLs, and targeting tumor cells and CAFs. These observations provide a new strategy for the clinical use of genetically modified tumor cells as cancer vaccines.