COSTIMULATION ENHANCES THE ACTIVE IMMUNOTHERAPY EFFECT OF RECOMBINANTANTICANCER VACCINES

Activation of T lymphocytes in the absence of a costimulatory signal c an results in anergy or apoptotic cell death. Two molecules capable of providing a costimulatory signal, B7-1 (CD80) and B7-2 (CD86), have b een shown to augment the immunogenicity of whole-tumor cell vaccines. To explore a potential role for costimulation in the design of recombi nant anticancer vaccines, we used lacZ-transduced CT26 as an experimen tal tumor and beta-galactosidase (beta-gal) as the model tumor antigen . Attempts to augment the function of a recombinant vaccinia virus (rV V) expressing beta-gal by admixture wit rVV expressing murine B7-1 wer e unsuccessful. However, a double recombinant vaccinia virus engineere d to express both B7-1 and the model antigen beta-gal was capable of s ignificantly reducing the number of pulmonary metastases when administ ered to mice bearing tumors established for 3 or 6 days. Most importan t, the double recombinant vaccinia virus prolonged the survival of tum or-bearing mice. These effects were antigen specific. The related cost imulatory molecule B7-2 was found to have a similar, although less imp ressive enhancing effect on the function of a rVV expressing beta-gal. Thus, the addition of B7-1 and, to a lesser extent, B7-2 to a rVV enc oding a model antigen significantly enhanced the therapeutic antitumor effects of these poxvirus-based, therapeutic anticancer vaccines.