Therapeutic properties of DNA-based fibroblast and dendritic cell vaccines in mice with squamous carcinoma

Dendritic cells (DC) express class I/II MHC-determinants and co-stimulatory molecules required for T cell activation. In a mouse model of squamous cell carcinoma (SCC), we compared the immunogenic properties of allogeneic DNA-based fibroblast vaccines, which are taken up and processed by DC of the host, and syngeneic DNA-based DC vaccines, which present antigens directly. The incentive was the important practical advantages of using fibroblasts rather than DC in generating vaccines for the immunotherapy of SCC.

The fibroblast vaccine was prepared by transfer of genomic DNA-fragments (25 kb) from relatively small numbers (10(7) = 64 mm3 tumor) of SCCVII/SF cells into LM cells, a mouse fibroblast cell line (H-2(k)). SCCVII/SF cells are a highly aggressive squamous carcinoma cell line of C3H/He mouse origin (H-2(k)). As the transferred DNA spontaneously integrates into the genome of the recipient cells, and is replicated as the cells divide, the number of transfected fibroblasts could be conveniently expanded for repeated immunizations. Syngeneic DC, rather than fibroblasts, were also used as the recipients of DNA from the SCC. C3H/He mice, highly susceptible to growth of SCCVII/SF cells, were immunized with either the DNA-based fibroblast or the DNA-based DC vaccine and the antitumor immune responses were compared.

Robust CD8+ T cell-mediated antitumor immunity sufficient to deter the growth of the neoplastic cells was generated in mice immunized with the transfected fibroblasts, but not in mice immunized with the transfected DC.

These data raise the possibility that an analogous strategy could be used to treat squamous carcinoma patients with minimal residual disease after primary therapy.