Antitumor Vaccination with Gene-Transduced Tumor Cells Expressing a Fusion Protein RM4/IFN-τ

Abstract

Our previous studies showed that secretion of a fusion protein RM4/IFN-τ from a mouse myeloma cell line V_KC_K/RM4-IFN-τ curtailed its tumorigenicity. Inoculation of V_KC_K/RM4-IFN-τ tumor cells further induced a protective immunity against a secondary challenge of parental V_KC_K tumor cells, in which the predominant immune cellular components are CD8⁺ T cells. In this study, V_KC_K/RM4-IFN-τ cell line was again used to further characterize the protective immunity. We found that the reduced tumorigenicity of V_KC_K/RM4-IFN-τ was directly related to the amount of fusion protein secreted by tumor cells, and that CD8⁺ T cells derived from mice experienced with V_KC_K/RM4-IFN-τ tumor regression played an important role in the protective immunity in a chromium release assay in vitro and in an animal study in vivo by using T-cell subset depleted mice. Our animal studies also showed that not only the cytotoxic but also the memory T cells against the secondary challenge of parental V_KC_K cells could be adoptively transferred to normal BALB/c mice. In addition, our animal studies further showed that local vaccination of irradiated V_KC_K/RM4-IFN-τ cells was able to significantly inhibit established tumors in early stages in vivo. This study thus highlights the potential utility of this engineered V_KC_K/RM4-IFN-τ tumor cells secreting the fusion protein RM4/IFN-τin cancer gene therapy.