ACTIVE IMMUNOTHERAPY OF CANCER WITH A NONREPLICATING RECOMBINANT FOWLPOX VIRUS ENCODING A MODEL TUMOR-ASSOCIATED ANTIGEN

Some tumor cells express Ags that are potentially recognizable by T ly mphocytes and yet do not elicit significant immune responses. To explo re new immunotherapeutic strategies aimed at enhancing the recognition of these tumor-associated Ags (TAA), we developed an experimental mou se model consisting of a lethal clone of the BALB/c tumor line CT26 de signated CT26.WT, which was transduced with the lacZ gene encoding bet a-galactosidase, to create CT26.CL25. The growth rate and lethality of CT26.CL25 and CT26.WT were virtually identical despite the expression by CT26.CL25 of the model tumor Ag in vivo. A recombinant fowlpox vir us (rFPV), which is replication incompetent in mammalian cells, was co nstructed that expressed the model TAA, beta-galactosidase, under the influence of the 40-kDa vaccinia virus early/late promoter. This recom binant FPV.bg40k, functioned effectively in vivo as an immunogen, elic iting CD8(+) T cells that could effectively lyse CT26.CL25 in vitro. F PV.bg40k protected mice from both subcutaneous and intravenous tumor c hallenge by CT26.CL25, and most surprisingly, mice bearing established 3-day pulmonary metastasis were found to have significant, Ag-specifi c decreases in tumor burden and prolonged survival after treatment wit h the rFPV. These observations constitute the first reported use of rF PV in the prevention and treatment of an experimental cancer and sugge st that changing the context in which the immune system encounters a T AA can significantly and therapeutically alter the host immune respons e against cancer.