Antibody-dependent antitumor cytotoxicity by human monocytes cultured with recombinant macrophage colony-stimulating factor. Induction of efficient antibody-mediated antitumor cytotoxicity not detected by isotope release assays.
Macrophage colony-stimulating factor (M-CSF) is known to stimulate proliferation of monocyte/macrophage progenitors and enhance in vitro antitumor cytotoxicity by murine macrophages. In this paper we have shown that recombinant human M-CSF causes human peripheral blood monocytes to differentiate in culture into metabolically active macrophage-like cells. These cells mediate very efficient antibody-dependent cellular cytotoxicity (ADCC) against human melanoma and neuroblastoma cell lines in the presence of two murine IgG3 mAbs (3F8 and R24). They also mediate antibody-independent cytotoxicity (or cytostasis) to a lesser extent. Human serum had an inconsistent effect on ADCC, but often induced similar high levels of ADCC. Cytotoxicity was measured using a novel ELISA to detect surviving tumor cells after ADCC. Two conventional isotope-release assays (51Cr and [3H]TdR) underestimated or entirely failed to detect ADCC by M-CSF-activated monocytes. Optimal activation occurred with 100-300 U/ml of M-CSF, and required 9-11 d for completion. Most of the M-CSF cultured monocytes expressed the low-affinity Fc receptor (CD16). ADCC by cells of the monocyte/macrophage lineage using murine IgG3 mAbs may have significance for the immunotherapy of human malignancies.
Munn
D H
DH
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Cheung
N K
NK
D000920:Antibody-Dependent Cell Cytotoxicity; D000943:Antigens, Differentiation / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D002454:Cell Differentiation; D002470:Cell Survival; D002860:Chromium Radioisotopes / Q000378:metabolism; D003115:Colony-Stimulating Factors / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005732:Gangliosides / Q000276:immunology; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor; D009000:Monocytes / Q000145:classification / Q000166:cytology / Q000276:immunology*; D011961:Receptors, Fc / Q000032:analysis; D017452:Receptors, IgG; D011994:Recombinant Proteins; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000943:Antigens, Differentiation; D015214:Antigens, Differentiation, Myelomonocytic; D002860:Chromium Radioisotopes; D003115:Colony-Stimulating Factors; D005732:Gangliosides; D007141:Immunoglobulin Fc Fragments; D011961:Receptors, Fc; D017452:Receptors, IgG; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D013936:Thymidine