IFN-ALPHA(1) GENE TRANSFECTION COMPLETELY ABOLISHES THE TUMORIGENICITY OF MURINE B16 MELANOMA-CELLS IN ALLOGENEIC DBA/2 MICE AND DECREASES THEIR TUMORIGENICITY IN SYNGENEIC C57BL/6 MICE

The murine B16 melanoma (H-2(b)) was transfected with a retroviral vector containing the mouse IFN-alpha(1) gene. IFN-alpha(1)-transfected cells produced IFN-alpha in vitro and exhibited an altered phenotype characterized by a decreased rate of multiplication, enhanced expression of H-2 antigens, an antiviral state to VSV, and decreased pigmentation. Control and IFN-alpha(1)-transfected cells were tested for their ability to grow in syngeneic: (H-2(b)) C57B1/6 and allogeneic (H-2(d)) DBA/2 mice. IFN-alpha(1)-producing B16 clones were less tumorigenic after s.c., i.p., and i.v. routes of injection than IFN-non-producer B16 clones in syngeneic C57B1/6 mice. IFN-alpha(1)-producing B16 cells were, however, totally rejected by allogeneic DBA/2 mice regardless of the routes and inocula tested, while control B16 cells grew in and killed DBA/2 mice. The total rejection of IFN-alpha(1)-transfected B16 cells in allogeneic mice appeared to be dependent on T cells as these cells grew in DBA/2 nude mice. Incubation of IFN-alpha-producing clones with anti-mouse IFN-alpha/beta prior to injection into C57B1/6 mice did not enhance their tumorigenicity. Likewise, injection of C57B1/6 and DBA/2 mice with antibody to IFN-alpha/beta did not enhance the tumorigenicity of IFN-alpha(1)-transfected cells. C57B1/6 mice immunized with irradiated IFN-alpha(1) cells were only slightly protected against a subsequent challenge with parental B16 cells. In contrast, DBA/2 mice immunized with irradiated IFN-alpha(1) cells exhibited tumor-specific, long-lasting immunity to subsequent challenge with parental B16 cells. (C) 1995 Wiley-Liss, Inc.