Tumor recurrence after partial hepatectomy for liver metastases in rats: prevention by in vivo injection of irradiated cancer cells expressing GMCSF and IL-12.
BACKGROUND
Adjuvant treatment could be helpful in prevent recurrence after partial hepatectomy for liver metastases. The purpose of this study was to assess the benefit of in vivo injection of irradiated autologous cancer cells expressing cytokines after partial hepatectomy in rats.


METHODS
Fifty-four BDIX rats were injected with 3 x 10(6) DHD-K12 cancer cells into the portal vein to induce multiple hepatic metastases. A 70% hepatectomy was carried out 3 days after the injection. The rats were then randomized into three groups of 18 rats each. Rats were given three injections at days 8, 15, and 21 of 5 x 10(6) irradiated DHD-K12 cancer cells expressing either interleukin 12 (IL-12) (group 1), granulocyte monocyte colony stimulating factor (GM-CSF) (group 2), or only saline solution (control group). At day 30, animals of each group were divided into two subgroups: 10 rats of each group were killed for pathological examination and cytofluorimetric analysis and 8 rats of each group were maintained for survival follow-up.


RESULTS
At day 30, mean number of tumors on liver surface was lower in rats treated by irradiated cancer cells expressing IL-12 than those in GM-CSF group or in the control group. Furthermore, peritoneal carcinomatosis was significantly more frequent in the control group: 3/9 (33%) than in pooled IL-12 and GM-CSF groups: 1/19 (5%) (P < 0.05). In the survival study, we observed a significant increased survival in treated rats compared with the control group (P = 0.0008).


CONCLUSIONS
Our results suggest that vaccination with autologous irradiated cancer cells expressing either IL-12 or GM-CSF induced a systemic immune antitumoral response that may be useful as an adjuvant therapy after surgical resection for liver metastases.
Aussilhou
Béatrice
B
Department of Surgery, Hospital Beaujon-Université Paris VII, Clichy, France.
Panis
Yves
Y
Alves
Arnaud
A
Nicco
Carole
C
Klatzmann
David
D
D000818:Animals; D002277:Carcinoma / Q000378:metabolism / Q000556:secondary / Q000628:therapy*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D003131:Combined Modality Therapy; D005434:Flow Cytometry; D005720:Gamma Rays; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006498:Hepatectomy; D016233:Immunotherapy, Active / Q000379:methods*; D007275:Injections, Intravenous; D018664:Interleukin-12 / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000556:secondary / Q000628:therapy*; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D051381:Rats
D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor