Macrophage colony-stimulating factor enhancement of antibody-dependent cellular cytotoxicity against human colon carcinoma cells.
Antibody-dependent cellular cytotoxicity (ADCC) has been suggested to be an important defense mechanism against tumors. The effects of recombinant human macrophage colony-stimulating factor (rhM-CSF) on ADCC activity of human monocytes were investigated. Human peripheral monocytes were pre-incubated for 72 h with rhM-CSF at various concentrations (50, 100, 200, 400 U/ml) and then used as effector cells in a 24-h 111-Indium release assay. Human carcinoma cell lines LS-174T, CBS, and KLE were used as targets to react with anti-carcinoma monoclonal antibodies (mAbs: murine D612, murine CC49, and chimeric CC49). A significant increase in ADCC activity was observed after monocytes were incubated in 100-400 U/ml of human rhM-CSF. Variation in ADCC activity of monocytes among donors was observed. The enhancement of ADCC activity was blocked by the addition of a neutralizing antibody to rhM-CSF. Less D612 mAb was required for the rhM-CSF-treated monocytes to mediate an equivalent level of ADCC activity as compared to the untreated monocytes. Because of the low levels of rhM-CSF required in these studies to enhance ADCC, treatment of monocytes alone with comparable levels of rhM-CSF did not enhance antibody-independent cytotoxicity. Moreover, it is demonstrated here that recombinant human interleukin-4 (rhIL-4) and rhM-CSF can have a synergistic effect of monocyte-mediated ADCC on human tumor cells. These results thus indicate that rhM-CSF augments ADCC of human peripheral blood monocytes using mAbs to human carcinomas, suggesting a potential role for rhM-CSF in cancer immunotherapy.
Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD 20892, USA.
C F
CF
Qi
C
C
Nieroda
R
R
De Filippi
J W
JW
Greiner
P
P
Correale
J
J
Schlom
K Y
KY
Tsang
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D018845:CD11 Antigens / Q000276:immunology; D019002:CD56 Antigen / Q000276:immunology; D002277:Carcinoma / Q000276:immunology* / Q000628:therapy; D003110:Colonic Neoplasms / Q000276:immunology* / Q000628:therapy; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D008212:Lymphocyte Depletion; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D019002:CD56 Antigen; D011994:Recombinant Proteins; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor