Delivery of interleukin-12 in gelatin hydrogels effectively suppresses development of transplanted colonal carcinoma in mice

Purpose: The sustained effects of interleukin-12 (IL-12) incorporated in biodegradable hydrogel on the development of transplanted colon carcinoma were investigated in C57BC/6 N mice. Methods: IL-12 was given to the animals incorporated in gelatin hydrogels (GH) which allow its gradual release. As the control administration, IL-12 was given via two subcutaneous injections at an interval of 6 days. Growth of the tumors was evaluated in terms of volume. Results: When IL-12 at 500 ng/animal was administered in GH, the tumor volume was decreased 9 and 12 days after administration, and the response was dose dependent in the range 0-500 ng/animal. The effect of IL-12 was stronger in mice treated with GH than in mice treated by subcutaneous injection at the same dose (i.e. 250 ng/animal twice at an interval of 6 days). Feeding behavior and the post-mortem wet weight of several visceral organs were unchanged after IL-12 administration. Serum parameters relative to the liver, heart and kidneys were unaffected by IL-12 treatment. No noticeable toxicity was detected when the dose of IL-12 in GH was increased to 1000 ng/animal. Conclusions: The results suggest that IL-12 is effective in suppressing the growth of colon carcinoma, and that delivery of this agent in GH is efficient in the treatment of carcinoma.