Lymphokine-activated killer (LAK) cell purging of leukemic bone marrow: range of activity against different hematopoietic neoplasms.
Natural killer cells activated in vitro by incubation with IL-2 display a broad range of cytolytic activity against neoplastic cells. These lymphokine-activated killer (LAK) cells can discriminate between neoplastic and normal bone marrow cells and may represent a useful means of purging bone marrow prior to autologous transplantation. We demonstrate that LAK cells can successfully remove four distinctly different malignant hematopoietic cell types from normal bone marrow grafts. The LAK purging technique is capable of a 2-3 log10 reduction in tumor cells in the bone marrow graft without compromising hematological recovery or survival. Our results also suggest, however, that an inhibitory effect on stem cell function by allogeneic LAK cells exists, and this form of purging may be used only if greater levels of bone marrow are transferred in an allogeneic setting. The ability to detect and eliminate malignant cells in bone marrow prior to use for autologous transplantation suggests that LAK cells, alone or in conjunction with current methods of bone marrow purging, could be useful for the in vitro treatment of bone marrow in patients who require high-dose chemotherapy and autologous bone marrow transplantation.
Long
G S
GS
Department of Pathology, University of Pittsburgh School of Medicine.
Cramer
D V
DV
Harnaha
J B
JB
Hiserodt
J C
JC
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D001853:Bone Marrow / Q000473:pathology*; D016026:Bone Marrow Transplantation / Q000473:pathology; D003602:Cytotoxicity, Immunologic; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D007942:Leukemia, Experimental / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D014411:Neoplastic Stem Cells / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN / Q000276:immunology; D011916:Rats, Inbred F344 / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000473:pathology; D014182:Transplantation, Autologous
D000943:Antigens, Differentiation; D007376:Interleukin-2