| Abstract: |
Summary. We conducted experiments to determine the optimal conditions for colony‐stimulating factor‐enhanced neutrophil‐ and mononuclear phagocyte‐mediated antibody‐dependent cell‐mediated cytotoxicity (ADCC) using monoclonal antibodies to disialogangliosides expressed on neuroectodermal tumour target cells. Neutrophil ADCC was most effective at effector: target ratios of 100:1, with maximal cytotoxic responses to melanoma target cells generated by 3 h. Granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and granulocyte colony‐stimulating factor (G‐CSF) were the most potent stimulators of neutrophil ADCC, and enhanced ADCC activity was inhibited in the presence of antibody to Fc receptor type II (FcRII). GM‐CSF and macrophage colony‐stimulating factor (M‐CSF) treatment of freshly isolated monocytes inhibited antibody‐independent cytotoxicity but enhanced antibody‐dependent responses. After 3 d in culture with CSF, 3–10‐fold enhancement of ADCC against melanoma target cells was observed at effector: target cell ratios of 10:1. Greatest stimulation of macrophage ADCC was obtained when GM‐CSF, M‐CSF or interleukin 3 (IL‐3) were used in conjunction with a secondary stimulus. Although gamma interferon (γ‐IFN) did not augment the cytotoxic capability of GM‐CSF‐ and IL‐3‐stimulated macrophages, prominent cytotoxic enhancement was seen when M‐CSF‐stimulated macrophages were exposed to γ‐IFN. A chimaeric mouse/human monoclonal antibody was found to be equivalent in activity to the murine antibody in neutrophil ADCC; however, in macrophage ADCC assays with submaximal effector cell stimulation, the chimaeric antibody was associated with a two‐fold greater response. These studies indicate that under specific conditions, CSFs capable of increasing the number and functional activity of mature myeloid effector cells enhance antibody‐dependent cytotoxicity to neuroectodermal tumour target cells. Copyright © 1993, Wiley Blackwell. All rights reserved |
| Keywords: |
controlled study; human cell; melanoma; granulocyte macrophage colony stimulating factor; tumor cells, cultured; monoclonal antibody; gamma interferon; neuroblastoma; neutrophils; immunostimulation; monocytes; macrophages; granulocyte colony stimulating factor; granulocyte colony-stimulating factor; neuroectoderm tumor; colony-stimulating factors; colony stimulating factor 1; antibody dependent cellular cytotoxicity; granulocyte-macrophage colony-stimulating factor; interleukin 3; interleukin-3; dose-response relationship, immunologic; macrophage colony-stimulating factor; antibody-dependent cell cytotoxicity; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.
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