Allogeneic cell-mediated immunotherapy for eradication of minimal residualdisease: Comparison of T-cell and IL-2 activated killer (LAK) cell-mediated adoptive immunotherapy in murine models

In the course of allogeneic bone marrow transplantation (BMT), avoiding gra ft-versus-host disease (GVHD) while retaining the antileukemic effects of t he T cells remains a major challenge, T-cell depletion (TCD) reduces the in cidence of GVHD but increases the relapse rate after allogeneic BMT, We att empted to develop a regimen that would retain or increase the graft-versus- leukemia effect induced by donor T cells while preventing GVHD, Immunosuppr essed mice were given immunocompetent donor cells, i.e., fresh lymphocytes or lymphokine-activated killer (LAK) cells differing from the host in major (MHC) or minor (MiHC) histocompatibility antigens, Engraftment of donor ce lls was documented by polymerase chain reaction analysis. Administration of MHC- and MiHC-incompatible allogeneic LAK cells, especially in conjunction with recombinant interleukin-2 (rIL-2), increased disease manifestations a nd mortality associated with GVHD, On the other hand, irradiated LAK cells or TCD-LAK cells prevented GVHD in both mice models studied, Phenotypic ana lysis of LAK cells demonstrated that CD8(+)-equivalent (Lyt-2) T cells are of significance in aggravation of GVHD, The in vitro cytotoxic capacity of LAK cells against MHC-nonrestricted target cells was not reduced by either irradiation or TCD, These results provide the background for designing impr oved protocols for immunotherapy of residual disease after BMT. In addition , the data imply that antitumor effects may be retained by irradiated rIL-2 -activated allogeneic cells without causing GVHD, Whereas unmodified alloge neic LAK cells can induce more effective graft-versus-leukemia effects at t he cost of GVHD, irradiated allogeneic donor LAK cells might play some role in eradication of minimal residual disease following autologous or allogen eic BMT without causing GVHD, (C) 1999 International Society for Experiment al Hematology. published by Elsevier Science Inc.