Lymphokine-activated killer cells selectively kill tumor cells in bone
marrow without compromising bone marrow stem cell function in vitro
MR van den Brink, PJ Voogt, WA Marijt, SA van Luxemburg-Heys, JJ van Rood and A Brand
Department of Immunohematology, University Medical Center of Leiden, The
Netherlands.
Although it has been demonstrated that lymphokine-activated killer (LAK)
cells kill tumor cells in a selective way without being toxic to a variety
of normal cells, contradictory results exist about the possible toxicity of
natural killer (NK) and LAK cells for hematopoietic progenitor cells.
Therefore, the cytolytic activity and growth inhibitory effects of LAK
cells on normal bone marrow progenitor cells and the ability of LAK cells
to eliminate neoplastic hematopoietic cells from populations of bone marrow
cells in vitro was studied. The results of these experiments show the
following: (1) LAK cells have little cytolytic activity against normal bone
marrow cells; (2) normal bone marrow cells fail to cold target compete for
the killing of the hematopoietic tumor cell lines K562 and HL60 or freshly
frozen acute myelocytic leukemia (AML) blast cells by LAK cells; (3) LAK
cells inhibit the growth of K562 and HL60 to more than 90% in clonogenic
assays; (4) LAK cells have no inhibitory effect on hematopoietic progenitor
growth in CFU-GM (colony-forming unit- granulocytes, macrophages), CFU-E
(colony-forming unit-erythrocytes), BFU-E (burst-forming
units-erythrocytes), or CFU-GEMM (colony-forming unit-granulocytes,
erythrocytes, macrophages, megakaryocytes) assays. These results indicate
that LAK cells have low toxicity for normal bone marrow and that LAK
activity against tumor cells is not adversely affected by the presence of
normal bone marrow cells. The differences in cytolysis and growth
inhibition of neoplastic hematopoietic cells and hematopoietic progenitor
cells by LAK cells in vitro could create a therapeutic index that might
allow the use of LAK cells for cleansing of the autologous bone marrow
graft and for adjuvant therapy in combination with autologous bone marrow
transplantation without compromising the reconstitution of the bone marrow
in the host.
Volume 74,
Issue 1,
pp. 354-360,
07/01/1989
Copyright © 1989 by The American Society of Hematology