Proliferation of human malignant hematopoietic cells in immunodeficient mice: suppression by antibody to pluripotent K-562 leukemia cells involves direct cytolysis and effector cells.
Six human hematopoetic cell lines were successfully heterotransplanted into athymic (nude) and asplenic-athymic (lasat) neonatal mice. The tumors arising from leukemia and lymphoma cells could then be serially transplanted into adult nude mice. Seven days after the fourth serial mouse passage, each mouse was treated with goat immune gamma globulin against K-562 cells. One control group was treated similarly, but with nonimmune (normal) gamma globulin, while another control group was not treated. The goat gamma globulin was not toxic for nude and lasat mice, and the immune, but not the normal, gamma globulin suppressed local subcutaneous growth of myelosarcomas, lymphosarcomas, and Burkitt lymphoma cells. On the other hand, the growth of lung, breast, and prostatic carcinomas and a melanoma of human origin were not altered by the immune gamma globulin. Since suppression of cell growth occurred equally well in decomplemented mice, a complement-mediated cytotoxicity apparently cannot be considered as responsible for the abrogation. The Fab fragment of the immunoglobulin did not suppress the growth of the myelosarcomas. We conclude that antibody suppression of the in vivo proliferation was specific for malignant hematopoietic cells and that the Fc portion of IgG is necessary for in vivo cytolysis of leukemia cells. The most probable mechanisms are direct antibody cytolysis and antibody-dependent macrophage-mediated cytotoxicity.
D000230:Adenocarcinoma / Q000276:immunology; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D000951:Antigens, Neoplasm / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology; D002283:Carcinoma, Bronchogenic / Q000276:immunology; D006041:Goats / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007106:Immune Sera; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007621:Karyotyping; D007938:Leukemia / Q000276:immunology; D008223:Lymphoma / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000276:immunology; D012910:Snake Venoms / Q000276:immunology; D014183:Transplantation, Heterologous
D000951:Antigens, Neoplasm; D007106:Immune Sera; D007141:Immunoglobulin Fc Fragments; D012910:Snake Venoms