Enhancement of Antitumor Transplantation Resistance in Rats by Appropriately Timed Administration of Busulfan1

Enhancement of specific transplantation resistance to a syngeneic tumor (KMT-17) was observed in WKA rats by treatment with the antileukemia drug busulfan (BU) (15 mg/kg) 5 days before and 5 days after immunization with X-irradiated KMT17 tumor cells. Rats immunized with X-irradiated KMT-17 cells and then treated with BU showed specific transplantation re sistance only against KMT-17 tumor. Carrageenan administra tion after BU treatment had no effect on enhancement by BU, which indicated that macrophages were not playing a major role in the observed enhancement. With the Winn assay, it was found that spleen cells from rats immunized with X-irradiated tumor cells followed by BU inhibited the growth of admixed tumor cells more strongly than did spleen cells from rats only immunized or only BU treated and that the tumor-neutralizing activity of spleen cells from rats treated by immunization fol lowed by BU was abrogated by treatment with anti-T-serum and complement. It was suggested that the enhanced antitumor transplantation resistance caused by BU was due to enhanced T-cell immune responses to tumor cells. Enhancement of antitumor transplantation resistance by BU was significantly abro gated by adoptive transfer with thymus cells and was slightly abrogated with spleen cells from rats immunized with X-irradi ated KMT-17 cells 1 day before tumor challenge but receiving no other treatment. Transfer of sera from the immunized rats had no effect on enhancement by BU. These results, taken together, suggest that the mechanism of the enhancement by BU involved a selective elimination of the immunosuppressor cells from the immunized hosts.