Interleukin-2 in bone marrow transplantation: preclinical studies.
Interleukin-2 (IL-2) promotes the generation and proliferation of killer cells in the peripheral blood and bone marrow (BM) both in vitro and in vivo. When employed in a syngeneic bone marrow transplantation (BMT) setting and followed by IL-2 therapy, murine BM cells activated with IL-2 in vitro (ABM) demonstrate potent graft-versus-leukemia (GVL) and anticytomegalovirus effects. ABM cells retain the capacity to reconstitute the hemopoietic system both in normal and leukemic mice. This therapy does not cause graft-versus-host disease (GVHD). Human ABM cells carry out purging of leukemia without loss of progenitor cell activity in vitro. The purging ability of ABM can be augmented by interleukin-1, interferon, and tumor necrosis factor. IL-2 therapy stimulates the veto suppressor cell activity of T cell-depleted BM, and has reduced GVHD and permitted engraftment of mismatched allogeneic BM in murine models. Future studies should determine the optimum treatment schedules with IL-2 for improving the GVL effect in autologous BMT, and for abolishing GVHD in allogeneic BMT settings.
Charak
B S
BS
Bone Marrow Transplantation Program, Georgetown University, Washington, DC.
Choudhary
G D
GD
Tefft
M
M
Mazumder
A
A
D000818:Animals; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D016207:Cytokines / Q000494:pharmacology*; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000628:therapy*; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005544:Forecasting; D006086:Graft vs Host Disease / Q000209:etiology / Q000628:therapy*; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000628:therapy*; D051379:Mice
D016207:Cytokines; D007376:Interleukin-2