In vitro and in vivo assessment of the graft-versus-leukemia activity of cord blood.
Allogeneic bone marrow transplantation (BMT) frequently is accompanied by the occurrence of graft-versus-host disease (GVHD). GVHD is thought to mediate a beneficial graft-versus-leukemia (GVL) effect believed to be important for disease-free survival in cancer patients. However, it is uncertain if GVHD and GVL are mediated by unique effector cell populations in the graft. The lack of bone marrow donors for individuals needing HLA-matched, unrelated BMT has recently led to the use of cord blood for transplantation. Cord blood transplantation has generated much enthusiasm because of its very low incidence of GVHD, even in HLA-mismatched situations, owing to intrinsic defects in mature T cell functions. Concerns have arisen, however, as to whether cord blood would mediate a significant GVL activity in vivo in the absence of GVHD, and thus prevent relapse in patients treated for malignancies. In this study in vitro and in vivo assessments have been made of the ability of cord blood to mediate GVL activity, focusing on non-specific effector cell mechanisms. Although minimal non-specific cytotoxic activity is found in freshly isolated cord blood (both NK and LAK cell activity), it is rapidly induced and displays a spectrum of lytic activity similar to adult peripheral blood. The kinetics of LAK cell induction in cord blood as well as the responsiveness to IL-2 stimulation was identical to adult peripheral blood.(ABSTRACT TRUNCATED AT 250 WORDS)
Harris
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Department of Microbiology and Immunology, University of Arizona, Tucson 85721, USA.
D000328:Adult; D000818:Animals; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000097:blood* / Q000628:therapy; D006801:Humans; D007231:Infant, Newborn; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D007938:Leukemia / Q000097:blood* / Q000628:therapy; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D014407:Tumor Cells, Cultured