IL-15 May Offer Selective Chemoprotection: Animal Trials

BUFFALO, NY--Animal studies have shown that interleukin-15 (IL-15) effectively protects the host from chemotherapy-induced diarrhea, with maintenance of antitumor activity, said Youcef Rustum, PhD, of Roswell Park Cancer Institute, at the first meeting of the Regional Cancer Center Consortium for Biological Therapy of Cancer, hosted by Roswell Park.

In one trial, rats with advanced colorectal cancer were given either fluorouracil modulated by leucovorin or irinotecan (Camptosar) plus one of two doses of IL-15 as the chemoprotective cytokine.

The data in the rats given irinotecan showed two major effects of IL-15 protection (see table). In group IV, the smaller dose of IL-15 (100 µg/kg for 11 doses) offered complete protection against drug-related lethality. In group III, toxicity and subsequent death were increased in the group receiving the largest amount of IL-15 (eight 400 µg/kg doses).

"Thus, the optimal dose and schedule of IL-15 for protection against irinotecan-induced toxicity in this animal model is 100 µg/kg for 11 doses," he said.

The results for IL-15 protection were similar in the rats given fluorouracil and leucovorin. In addition, in these animals, IL-15 potentiated the antitumor activity of fluorouracil/leucovorin, resulting in an increased therapeutic index.

"In similar studies with IL-2, we observed that IL-2 injected daily into rats for 5 days did not protect from chemo-toxicity. Only the rats who received IL-15 were protected selectively from diarrhea," he said. Future studies should include clinical trials using IL-15 to lessen the severity of chemotherapy in cancer patients, Dr. Rustum concluded.