Treatment of murine hepatic metastases with vaccinia colon oncolysates and IL-2.
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 X 10(5) tumor cells and sacrificed 14 days following tumor challenge. In the second set of experiments, animals were challenged with 2 X 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 micrograms, 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 less than 0.0021), and IL-2 (P less than 0.0017). The data presented suggest a synergistic effect for these two agents.(ABSTRACT TRUNCATED AT 250 WORDS)
Barnavon
Y
Y
Department of Surgery, Mount Sinai Medical Center, Miami Beach, Florida.
Iwaki
H
H
Bash
J A
JA
Brettschneider
F
F
Hilsenbeck
S
S
Darnell
E
E
Wallack
M K
MK
D000230:Adenocarcinoma / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D000818:Animals; D003110:Colonic Neoplasms / Q000382:microbiology; D003131:Combined Modality Therapy; D005260:Female; D007167:Immunotherapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000556:secondary; D014616:Vaccinia virus / Q000276:immunology; D014765:Viral Vaccines / Q000627:therapeutic use
D007376:Interleukin-2; D014765:Viral Vaccines