Therapy of murine leukemia with cyclophosphamide and immune Lyt-2+ cells: cytolytic T cells can mediate eradication of disseminated leukemia.
Several animal models have been developed in which the adoptive transfer of specifically immune syngeneic T cells has been shown to mediate the eradication of established tumors. In adoptive chemoimmunotherapy (ACIT) of disseminated FBL leukemia with cyclophosphamide and immune T cells, the major effector T cell has been shown to be a noncytolytic Lyt-1+2- T cell that mediates its therapeutic effect without the participation of CTL. Because studies in other models have suggested that CTL can mediate an anti-tumor effect, the efficacy of Lyt-2+ T cells rendered highly cytolytic before adoptive transfer in ACIT of disseminated FBL was examined. The results demonstrated that such CTL had a detectable but limited therapeutic effect in the treatment of FBL. Because this limited activity of transferred purified CTL might have reflected a requirement for helper T cells to produce IL 2 for promotion of the in vivo survival and proliferation of the CTL, the effect of administering IL 2 to tumor-bearing hosts after transfer of CTL was examined. A dose of IL 2 previously shown to induce in vivo proliferation of transferred T cells rendered CTL that were minimally effective alone curative in ACIT of FBL leukemia. Thus, either lymphokine-producing T cells or the lymphokines produced by these cells are necessary for the full expression of the in vivo therapeutic potential of CTL.
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000950:Antigens, Ly / Q000008:administration & dosage / Q000276:immunology*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D007116:Immunization, Passive / Q000379:methods; D007376:Interleukin-2 / Q000008:administration & dosage; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification / Q000276:immunology / Q000637:transplantation*
D000276:Adjuvants, Immunologic; D000950:Antigens, Ly; D007376:Interleukin-2; D003520:Cyclophosphamide