title: Near eradication of clinically relevant concentrations of human tumor cells by interferon-activated monocytes in vitro.
abstract: We have previously reported that low concentrations of interferon (IFN)-activated monocytes exert near-eradicative cytocidal activity against low concentrations of several human tumor cells in vitro. In the present study, we examined 7 human tumor cell lines and 3 diploid lines in the presence or absence of 10 ng/mL IFNα2a and monocytes. The results confirmed strong cytocidal activity against 4 of 7 tumor lines but none against 3 diploid lines. To model larger in vivo tumors, we increased the target cell concentration and determined the concentration of IFNα2a and monocytes, required for cell death. We found that increasing the tumor cell concentration from 10- to 100-fold (10(5) cells/well) required an increase in the concentration of IFNs by over 100-fold and monocytes by 10-fold. High concentrations of monocytes could sometimes kill tumor or diploid cells in the absence of IFN. We may conclude that killing of high concentrations of tumor or diploid cells required high concentrations of monocytes that could sometimes kill in the absence of IFN. Thus, high concentrations of tumor cells required high concentrations of IFN and monocytes to cause near eradication of tumor cells. These findings may have clinical implications.
authors.affiliation: Cytokine Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Baron
authors.forename: Joel
authors.initials: J
authors.lastname: Finbloom
authors.forename: Julie
authors.initials: J
authors.lastname: Horowitz
authors.forename: Joseph
authors.initials: J
authors.lastname: Bekisz
authors.forename: Angel
authors.initials: A
authors.lastname: Morrow
authors.forename: Tongmao
authors.initials: T
authors.lastname: Zhao
authors.forename: Samuel
authors.initials: S
authors.lastname: Fey
authors.forename: Hana
authors.initials: H
authors.lastname: Schmeisser
authors.forename: Corey
authors.initials: C
authors.lastname: Balinsky
authors.forename: Kotaro
authors.initials: K
authors.lastname: Miyake
authors.forename: Christopher
authors.initials: C
authors.lastname: Clark
authors.forename: Kathryn
authors.initials: K
authors.lastname: Zoon
mesh_terms: D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D054796:Drug Dosage Calculations; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D016260:Monocytes, Activated Killer / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology
chemical_list: C554331:Ifna2 protein, mouse; D016898:Interferon-alpha