THERAPEUTIC EFFECT OF A VACCINIA COLON ONCOLYSATE PREPARED WITH INTERLEUKIN-2-GENE ENCODED VACCINIA VIRUS STUDIED IN A SYNGENEIC CC-36 MURINE COLON HEPATIC METASTASIS MODEL

Vaccinia CC-36 murine colon oncolysate (VCO) prepared with interleukin -2-gene encoded recombinant vaccinia virus (IL-2VCO) was used in the t reatment of a syngeneic murine colon adenocarcinoma (CC-36) hepatic me tastasis to test the beneficial effect of the interleukin-2-gene encod ed vaccinia virus over a control recombinant vaccinia virus in produci ng a vaccinia oncolysate tumor cell vaccine. Results suggest that the IL-2VCO treatment significantly reduced the hepatic tumor burden in co mparison with the controls that received either IL-2-gene-encoded reco mbinant vaccinia virus or a plain recombinant vaccinia virus or vaccin ia oncolysate prepared with the plain recombinant virus. The survival of mice treated with IL-2VCO was also improved in comparison with mice treated with other preparations. The induction of a cytolytic T lymph ocyte response was examined to elucidate the mechanism of the inductio n of antitumor responses in IL-2VCO-treated mice. Fresh peripheral blo od lymphocytes (PBL) isolated from IL-2VCO-treated mice showed a highe r cytolytic activity against CC-36 tumor cell target when compared to PBL from the mice of other treatment groups, suggesting that the IL-2V CO induced an antitumor cytolytic T lymphocyte response. These results suggest that a vaccinia oncolysate, prepared with recombinant vaccini a virus encoding an immunomodulating cytokine gene will enhance antitu mor responses in the host.