Treatment of murine hepatic metastases with vaccinia colon oncolysates and IL-2

Abstract

To evaluate the feasibility and utility of vaccinia colon oncolysates (VCO) and low-dose interleukin-2 (IL-2) immunotherapy for advanced colon cancer, we have developed a murine model and tested the efficacy of combined treatment regimens. We employed intrasplenic injection of cultured colon adenocarcinomas (C-C36) in syngeneic Balb/c mice to produce experimental hepatic metastases. In the first set of experiments, animals were challenged with 5 × 10 5 tumor cells and sacrificed 14 days following tumor challenge. In the second set of experiments, animals were challenged with 2 × 10 5 tumor cells and followed for survival over the ensuing 90 days. In the first set of experiments, animals were treated prophylactically with VCO (40 μg, sc, 14 and 7 days prior to challenge) and/or therapeutically with IL-2 (25,000 u, Hoffmann-LaRoche rIL-2, ip BID, on Days 1–3 following challenge). In the second set of experiments, animals were treated with either the identical regimens or therapeutically with VCO (same dose, sc, 2 and 10 days following challenge) and/or IL-2 (same dose, ip BID, on Days 9–11 following challenge). Tumor burden data from sacrificed animals was in agreement with survival data and showed significant tumor burden reduction in the combined treatment group as assessed by liver weight and tumor nodule enumeration. Survival data demonstrated highly significant survival advantage for animals treated with the two biological response modifiers: VCO ( P < 0.0021), and IL-2 ( P < 0.0017). The data presented suggest a synergistic effect for these two agents. By combining VCO with low-dose IL-2 therapy we hope to develop effective adjuvant therapy for advanced colon cancer patients and minimize the toxic side effects associated with high-dose IL-2 administration.