The
costimulatory molecule, B7-2, is expressed by various
lymphomas, but this level of expression is not sufficient to generate effective anti-
tumor immunity in vivo. To determine whether up-regulated expression of the
costimulatory molecule, B7-2, leads to more effective anti-
tumor immunity in vivo, the A20 murine model of
B-cell lymphoma was used. A20
tumor cells express major histocompatibility complex (MHC) I and II molecules and moderate constitutive levels of B7-2. While B7-1 and B7-2 have been introduced into
tumor cells lacking these molecules, studies have not been conducted to determine whether
tumors that constitutively express B7-1 or B7-2 can be made more immunogenic by increasing the expression of these molecules. In this report, A20/B7-2 transfectants expressing greater levels of B7-2 were rejected in syngeneic mice, and systemic immunity against the A20 parental cells was generated. Treatment with the A20/B7-2 variant cells significantly improved the survival of
tumor-bearing mice. Coinjection with
IL-12 secreting variants did not further augment the anti-
tumor immunity observed for B7-2
therapy alone. Both CD8(+) T cells and natural killer (NK) cells mediated the anti-
tumor immune response observed in A20/B7-2 immunized mice. In mice that developed
tumors after immunization with the A20/B7-2 variant cells, resected
tumor cells were shown to express lower levels of B7-2 than the transfected variants. These results suggest that the level of costimulation is important for the generation of anti-
tumor immunity and for host survival. In addition,
tumors appear to be able to evade the immune response by downregulating the expression of B7-2 below a threshold level.