IFN‐α 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‐α 1 gene. IFN‐α 1 ‐transfected cells produced IFN‐α 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‐α 1 ‐transfected cells were tested for their ability to grow in syngeneic (H‐2 b ) CS7B1/6 and allogeneic (H‐2 d ) DBA/2 mice. IFN‐α 1 producing B16 clones were less tumorigenic after s.c, i.p., and i.v. routes of injection than IFN‐non‐producer BI6 clones in syngeneic CS7B1/6 mice. IFN‐α 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‐α 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‐α‐producing clones with anti‐mouse IFN‐α/β prior to injection into C57BI/6 mice did not enhance their tumorigenicity. Likewise, injection of C57BI/6 and DBA/2 mice with antibody to IFN‐α/β did not enhance the tumorigenicity of IFN‐α 1 ‐transfected cells. C57B1/6 mice immunized with irradiated IFN‐α 1 cells were only slightly protected against a subsequent challenge with parental B16 cells. In contrast, DBA/2 mice immunized with irradiated IFN‐α 1 cells exhibited tumor‐specific, long‐lasting immunity to subsequent challenge with parental B16 cells. © 1995 Wiley‐Liss, Inc.