van den Brink M R, Voogt P J, Marijt W A, van Luxemburg-Heys S A, van Rood J J, Brand A
Department of Immunohematology, University Medical Center of Leiden, The Netherlands.
Blood. 1989 Jul;74(1):354-60.
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.
尽管已经证明淋巴因子激活的杀伤（LAK）细胞能以选择性方式杀伤肿瘤细胞，而对多种正常细胞无毒，但关于自然杀伤（NK）细胞和LAK细胞对造血祖细胞可能的毒性存在相互矛盾的结果。因此，研究了LAK细胞对正常骨髓祖细胞的细胞溶解活性和生长抑制作用，以及LAK细胞在体外从骨髓细胞群体中清除肿瘤性造血细胞的能力。这些实验结果如下：（1）LAK细胞对正常骨髓细胞几乎没有细胞溶解活性；（2）正常骨髓细胞不能通过冷靶竞争抑制LAK细胞对造血肿瘤细胞系K562和HL60或新鲜冷冻的急性髓细胞白血病（AML）原始细胞的杀伤；（3）在克隆形成试验中，LAK细胞将K562和HL60的生长抑制超过90%；（4）在CFU-GM（粒细胞、巨噬细胞集落形成单位）、CFU-E（红细胞集落形成单位）、BFU-E（红细胞爆式集落形成单位）或CFU-GEMM（粒细胞、红细胞、巨噬细胞、巨核细胞集落形成单位）试验中，LAK细胞对造血祖细胞生长没有抑制作用。这些结果表明，LAK细胞对正常骨髓的毒性较低，并且对肿瘤细胞的LAK活性不会受到正常骨髓细胞存在的不利影响。LAK细胞在体外对肿瘤性造血细胞和造血祖细胞的细胞溶解和生长抑制差异可能会产生一个治疗指数，这可能允许使用LAK细胞来净化自体骨髓移植物，并与自体骨髓移植联合用于辅助治疗，而不会损害宿主骨髓的重建。
