Chemo-adoptive immunotherapy against a guinea-pig leukemia

Summary Strain-2 guinea-pigs bearing the transplantable L₂C leukemia were treated with cytoxan 24 h prior to receiving an injection of either allogeneic or syngeneic spleen cells from donors preimmunized to the leukemia. Treatment with the drug alone produced a remission period which lasted for 4–5 weeks before eventual relapse and death. An IP transfer of spleen or peritoneal exudate (PE) cells from syngeneic strain-2 guinea-pigs hyperimmunized to the leukemia greatly extended the survival times of drug-treated animals beyond that observed in animals receiving normal strain-2 cells. Long-term survivors were refractory to a subsequent challenge with a lethal inoculum of L₂C cells. A reduced tumor load was essential for an immunotherapeutic effect of adoptively transferred cells. The use of sensitized lymphocytes alone failed to control the established disease. Hyperimmune spleen cells from strain-13 and Hartley guinea-pigs also demonstrated a slight capacity to inhibit the proliferation of leukemia cells when injected into diseased animals previously treated with the drug. Due to inadequate drug suppression, however, the injection of allogeneic cells from either immune strain-13 or Hartley guinea-pigs did not prolong the latent period for the appearance of the leukemia to the same extent as either immune strain-2 spleen or PE cells. A marked delay in the onset of disease was noted when immune spleen cells from either syngeneic or allogeneic sources were mixed in vitro with L₂C leukemia cells at a ratio of 200:1 before injection back into normal strain-2 animals. However, an exposure of L₂C blast cells in vitro with heat-inactivated serum obtained from L₂C-immune strain-2 animals significantly enhanced the onset of disease.