IMMUNIZATION WITH A SYNGENEIC TUMOR INFECTED WITH RECOMBINANT VACCINIA VIRUS EXPRESSING GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CSF) INDUCES TUMOR-REGRESSION AND LONG-LASTING SYSTEMIC IMMUNITY

A recombinant vaccinia virus encoding the gene for granulocyte-macroph age colony-stimulating factor (rV-GM-CSF) was used to infect the poorl y immunogenic murine colon adenocarcinoma cell line, MC-38. Infection of MC-38 tumor cells with rV-GM-CSF completely suppressed the growth o f the MC-38 primary tumors, whereas progressively growing tumors were formed in mice injected with MC-38 cells infected with wild type V-Wye th. Irradiation of the recipient B6 mice before implantation of rV-GM- CSF-infected tumor cells resulted in the development of progressively growing tumors. Moreover, in vivo T-cell depletion studies revealed th at growth suppression of the rV-GM-CSF-infected tumor cells was depend ent on the presence of both CD4(+) and CD8(+) T-cell subsets. Subseque nt studies established that this immunity was long-lasting and antigen specific, as demonstrated by the protection of rV-GM-CSF-immunized mi ce from MC-38 tumor challenge but not from challenge with another syng eneic tumor cell type. No such effects were observed when MC-38 tumor cells were infected with recombinant vaccinia viruses expressing inter leukin (IL)-2 or IL-6. The results demonstrate that paracrine release of biologically active murine GM-CSF by tumor cells infected with rV-G M-CSF enhances the intrinsic immunogenicity of a poorly immunogenic mu rine tumor. Presumably the augmentation of tumor immunogenicity induce s an antigen-specific T-cell-dependent antitumor response that prevent s the formation of primary tumors and protects mice from tumor challen ge. Thus in this experimental model, GM-CSF functions as a highly effe ctive vaccine adjuvant.