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

The therapeutic effect of ONO-4007, a new lipid A analog, was examined on t he 13762NF mammary adenocarcinoma in the F-344 rat system. Intravenous admi nistration of ONO-4007 (2.5 mg/kg) had a very potent effect on subcutaneous ly (s.c.) inoculated 13762NF tumor cells, but none at all on intravenously (i.v.) or intraperitoneally (i.p.) inoculated ones. Also no beneficial ther apeutic effect of ONO-4007 was observed on i.v. or i.p. inoculated tumor ce lls 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-al pha may be responsible in part for the beneficial effect of ONO-4007 agains t s.c. inoculated tumor cells. ONO-4007 may in the future become a useful m odality for the treatment of human cancers.