title: Natural killer (NK) cells as effectors of antibody-dependent cytotoxicity with chimeric antibodies reactive with human squamous-cell carcinomas of the head and neck.
abstract: In patients with cancer, antibody-dependent cellular cytotoxicity (ADCC) may be used as a laboratory test or for enhancing immunotherapy with murine monoclonal or chimeric mouse/human anti-tumor antibodies (mMAbs or cMAbs, respectively). We have established an ADCC assay with IgG1 cMAb SF-25, using human squamous-cell carcinoma of the head and neck (SCCHN) cell lines as targets. By flow cytometry, all SCCHN cell lines tested expressed the antigen recognized by cMAb SF-25. Trypsinization of the cell monolayers facilitated binding of cMAb SF-25 to the antigen on the cell surface of SCCHN targets. Using the PCI-50 SCCHN cell line as a target coated with this cMAb at the optimal concentration of 1.0 micrograms/ml, normal human peripheral blood mononuclear cells (PBMC, n = 28) were found to mediate ADCC at a mean level of 283 +/- 42 (SEM) lytic units (LU20/10(7) effector cells). Non-adherent monocyte-depleted PBMC and natural killer (NK) cells purified by negative selection mediated significantly higher levels of ADCC than unseparated PBMC against SCCHN targets. NK cells, defined as CD3-CD56+ cells, could be effectively armed by cMAb SF-25, as confirmed by flow cytometry and ADCC assays. IL2-activated armed NK cells mediated higher levels of ADCC than non-armed NK cells. Binding of cMAb SF-25 to NK cells and their ADCC were enhanced by pre-incubation with polyethylene glycol. Arming of NK cells with chimeric antibodies should be considered in developing novel strategies for treatment of human SCCHN, especially in the adjuvant setting.
authors.affiliation: Department of Otolaryngology, University of Pittsburgh School of Medicine, PA, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Sung
authors.forename: S
authors.initials: S
authors.lastname: Yasumura
authors.forename: J T
authors.initials: JT
authors.lastname: Johnson
authors.forename: G A
authors.initials: GA
authors.lastname: Van Dongen
authors.forename: T L
authors.initials: TL
authors.lastname: Whiteside
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007167:Immunotherapy; D007694:Killer Cells, Natural / Q000378:metabolism / Q000502:physiology*; D008856:Microscopy, Fluorescence; D011485:Protein Binding; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D007074:Immunoglobulin G