IL-12 gene therapy results in
tumor regression in some, but not all, murine models. We hypothesized that expression of B7.1 on the
tumor cell surface was necessary for IL-12-mediated
tumor regression. In addition, we hypothesized that all cells must express B7.1 for this to be effective. To evaluate this hypothesis,
tumor nodules were established in mice with either wild-type
B16 melanoma or with
B16 melanoma modified to express B7.1.
IL-12 cDNA was transferred to the
tumor by particle-mediated gene transfer. All
tumors modified to express B7.1 regressed completely after
IL-12 cDNA treatment. When the percent of B7.1-transfected B16 cells was decreased to 50%, no animals survived
after treatment. Animals rendered
tumor-free were then challenged with wild-type B16. Fifty percent of mice was protected from this
tumor challenge. Expression of CD28 (the stimulatory
B7.1 ligand) was significantly increased in both CD8(+) T cells and natural killer cell populations of mice rejecting
tumor challenge compared to mice with
tumor growth. These results suggest that the costimulatory molecule B7.1 is required for initial
tumor sensitivity to
IL-12 gene therapy and that protection from subsequent challenge with B7.1 (-)
tumor is mediated by CD28(+) immune effector cells.