Vaccinia colon oncolysate immunotherapy for murine hepatic metastases can be modulated with low-dose interleukin-2. Third place winner: Conrad Jobst Award.
A murine colon cancer hepatic metastases model was developed via intrasplenic injection of C-C36 tumor cells in syngeneic Balb/c mice to determine the potential efficacy of vaccinia colon oncolysate (VCO) immunoprophylaxis and therapy with and without low-dose interleukin-2 (IL-2) immunomodulation. Mice were injected with 40 micrograms VCO subcutaneously, either prophylactically or therapeutically. IL-2 (Hoffman-La Roche, Nutley, NJ) was administered at a dose of 25,000 units intraperitoneally twice daily for three consecutive days, prophylactically, therapeutically immediately after tumor challenge (early), or 9 days after tumor challenge (late). Mice were followed for 50 days after tumor challenge, and mortalities were recorded. Mice receiving VCO alone did not demonstrate better survival than controls. However, mice receiving VCO with IL-2 immunomodulation demonstrated consistently better survival than mice treated with IL-2 alone or controls. The group receiving VCO therapy with late IL-2 modulation (75% survival demonstrated improved survival over controls (0% survival, P less than 0.00001), VCO-treated mice (0% survival, P less than 0.005), and IL-2-treated mice (29% survival, P = 0.07). In vitro assays revealed enhanced NK activity and suggested cytotoxic T-lymphocyte (CTL) induction as possible mechanisms responsible for these biologic effects. Combined VCO and IL-2 immunotherapy may be of potential benefit to patients with metastatic colon cancer, but further research is required to optimize treatment regimens.
Barnavon
Y
Y
Department of Surgery, Mount Sinai Medical Center, Miami Beach, Florida.
Iwaki
H
H
Bash
J A
JA
Wallack
M K
MK
D000818:Animals; D003110:Colonic Neoplasms; D004195:Disease Models, Animal; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014407:Tumor Cells, Cultured; D014616:Vaccinia virus / Q000276:immunology*; D014765:Viral Vaccines / Q000627:therapeutic use*
D007376:Interleukin-2; D014765:Viral Vaccines