New immunotherapy for prevention of liver metastasis from colorectal cancer after surgery.

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(Experimental study) Donryu rats were inoculated with AH-130 tumor cells on day 0 via the portal vein, and 2 days later, IL-2 was administered continuously via the portal vein (P group), or into the subcutaneous space (S group). Control rats were received saline alone (C group). On day 8, the incidence of liver metastasis and cytotoxicities (NK, LAK and anti-AH-130 activity) of liver non-parenchymal cells (NPC), In P groups, hepatic metastasis were significantly reduced, and NK, LAK and anti-AH-130 activities of NPC were significantly augmented compared with C group. However, these effects were not observed in S group. LAK cells were induced from splenocytes and lymphocytes of the lymph nodes using ICR mice, cultured with IL-2. LAK cells cultured for 7 days showed about 70% of LAK activity.(Clinical study) We determined prostaglandin E2 (PGE2) (n=23) levels and lymphocyte subsets (n=10) in portal venous drainage of colorectal cancer. The PGE2 levels in the portal vein were significantly higher than those in the artery. Four of nine patients with more than 100pg/ml of portal PGE2 developed liver metastasis within two years following surgery. For prevention of recurrence in the liver, four patients with liver metastasis from colorectal cancer received intrahepatic combined immunotherapy using IL-2, OK-432, adriamycin, cyclophosphamide, and famotidine after hepatectomy. All patients are still alive more than 2 years. In conclusion, intrahepatic combined immunotherapy may be useful for prevention of liver metastasis from colorectal cancer. PGE2 levels in the portal vein may be anew predictor for liver recurrence from colorectal cancer.