Host-mediated therapeutic effects produced by appropriately timed administration of bleomycin on a rat fibrosarcoma

The timing of bleomycin (BLM) administration after KMT-17 tumor inoculation was found to be important for optimizing its therapeutic effect on tumor-bearing rats. A remarkable therapeutic effect was observed when BLM (5 mg/kg/day) was administered i.p. for 5 days from the eighth day after tumor inoculation (Day 8 to Day 12) rather than when BLM was administered i.p. for 5 days during the days immediately following tumor inoculation (Day 1 and Day 5) (cured rats/treated rats: 10/21 and 2/16, respectively). By means of a Winn assay, stronger tumor-neutralizing activities were observed in spleen cells from BLM (Day 8 to Day 12)-treated tumor-bearing rats than were observed in spleen cells from BLM (Day 1 to Day 5)-treated tumor-bearing rats (% Inhibition: 70.9 and 49.3%, respectively). These therapeutic effects were thus found to be consistent with the antitumor immunity against KMT-17. The enhanced tumor-neutralizing activities of spleen cells from BLM-treated tumor-bearing rats were suppressed by adding spleen cells from nontreated tumor-bearing rats. In cell transfer experiments, an antitumor transplantation resistance in rats immunized with irradiated KMT-17 cells was abrogated by an adoptive transfer of spleen cells from untreated tumor-bearing rats or BLM (Day 1 to Day 5)-treated tumor-bearing rats but not from BLM (Day 8 to Day 12)-treated tumor-bearing rats. These results suggest that, when BLM is administered during a late stage of tumor growth, it is effective in eliminating suppressor cells and that this leads to an improvement in the therapeutic effects of the drug.