title: Heterodimeric bispecific single-chain variable-fragment antibodies against EpCAM and CD16 induce effective antibody-dependent cellular cytotoxicity against human carcinoma cells.
abstract: A heterodimeric bispecific biological recombinant drug was synthesized by splicing DNA fragments from two fully humanized single-chain variable-fragment (scFV) antibody fragments forming a novel drug simultaneously recognizing the CD16 natural killer (NK) cell marker and the cancer marker epithelial cell adhesion molecule (EpCAM). The drug precipitously enhanced the killing of human carcinomas of the prostate, breast, colon, head, and neck even at very low effector:target ratios. The drug EpCAM16 rendered even nonactivated NK cell-proficient killers and activated them to kill via degranulation and cytokine production. Studies show that bispecific antibodies can be used to induce proficient killing of the carcinoma targets that ordinarily are resistant to NK-mediated killing. Apparently, the innate immune system can be effectively recruited to kill cancer cells using the bispecific antibody platform and EpCAM targeting.
authors.affiliation: 1 Section of Molecular Cancer Therapeutics, Therapeutic Radiology-Radiation Oncology, University of Minnesota Masonic Cancer Center , Minneapolis, Minnesota.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Vallera
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Gleason
authors.forename: Seunguk
authors.initials: S
authors.lastname: Oh
authors.forename: Louis M
authors.initials: LM
authors.lastname: Weiner
authors.forename: Dan S
authors.initials: DS
authors.lastname: Kaufman
authors.forename: Valarie
authors.initials: V
authors.lastname: McCullar
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Miller
authors.forename: Michael R
authors.initials: MR
authors.lastname: Verneris
mesh_terms: D018033:Antibodies, Bispecific / Q000494:pharmacology*; D000917:Antibody Formation; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology; D002277:Carcinoma / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology; D015550:Cell Degranulation; D045744:Cell Line, Tumor; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000276:immunology; D000071858:Epithelial Cell Adhesion Molecule; D006258:Head and Neck Neoplasms / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D009369:Neoplasms / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology*; D057127:Single-Chain Antibodies / Q000235:genetics / Q000494:pharmacology*
chemical_list: D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies; D007371:Interferon-gamma
keywords: ADCC; anti-CD16; bispecific antibody; carcinoma; human NK cells