Therapeutic effect of a new synthetic lipid A analog (ONO-4007) on a tumor implanted at different sites in rats.

The therapeutic effect of ONO-4007, a new lipid A analog, was examined on the 13762NF mammary adenocarcinoma in the F-344 rat system. Intravenous administration of ONO-4007 (2.5 mg/kg) had a very potent effect on subcutaneously (s.c.) inoculated 13762NF tumor cells, but none at all on intravenously (i.v.) or intraperitoneally (i.p.) inoculated ones. Also no beneficial therapeutic effect of ONO-4007 was observed on i.v. or i.p. inoculated tumor cells when it was combined with anticancer drugs such as carboplatin (CBDCA) or cyclophosphamide (CY). The therapeutic efficacy of ONO-4007 (2.5 mg/kg, 3 times a day for 6 days) for s.c. inoculated tumor cells was greater than that of CBDCA (20-30 mg/kg x 1), and it was also shown to stimulate spleen cells to produce tumor necrosis factor alpha (TNF-alpha) in vitro in a dose-dependent manner. These results suggest that enhanced production of TNF-alpha may be responsible in part for the beneficial effect of ONO-4007 against s.c. inoculated tumor cells. ONO-4007 may in the future become a useful modality for the treatment of human cancers.