Potential of autologous immunologic effector cells for bone marrow purging in patients with chronic myeloid leukemia.
Relapse is a major concern in autologous bone marrow transplantation (BMT). Therefore, purging of bone marrow to reduce the amount of tumor cells reinfused into the patient is widely used. Immunologic effector cells such as lymphokine activated killer (LAK) cells are attractive for purging of bone marrow since these cells might have an additional in vivo effect on tumor cells in contrast to other purging protocols. In patients with chronic myelogenous leukemia (CML), LAK cells can only be used in some patients for purging bone marrow since LAK cells possess no or only limited cytolytic activity against autologous CML tumor cells in most cases. In this study, we investigated the effect of autologous and allogeneic cytokine-induced killer (CIK) cells on tumor cells from patients with CML. CIK cells have been generated from peripheral blood lymphocytes by incubation with interferon-gamma on day 0, interleukin-1, interleukin-2 and a monoclonal antibody against CD3 on day 1. In contrast to LAK cells, CIK cells were able to lyse both autologous and allogeneic cells from patients with CML as determined by a 51Cr release and a tumor colony assay. The cytotoxicity of CIK cells against CML cells was confined to the CD56+ population. CIK cells showed no major toxic effect on hematopoietic progenitor cells when tested in CFU-GM assays. CIK cells eliminated three orders of magnitude of K562 cells and less than one order of magnitude of progenitor cells (25% reduction). This represents a differential effect of CIK cells on tumor and progenitor cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Scheffold
C
C
Abteilung Innere Medizin, Freie Universität Berlin, Germany.
Brandt
K
K
Johnston
V
V
Lefterova
P
P
Degen
B
B
Schöntube
M
M
Huhn
D
D
Neubauer
A
A
Schmidt-Wolf
I G
IG
D001483:Base Sequence; D016465:Bone Marrow Purging; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D008969:Molecular Sequence Data; D010641:Phenotype; D012313:RNA / Q000032:analysis / Q000235:genetics; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D012313:RNA