B7‐2 expression above a threshold elicits anti‐tumor immunity as effective as interleukin‐12 and prolongs survival in murine B‐cell lymphoma

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. © 2004 Wiley‐Liss, Inc.