title: Antibodies elicited by the first non-viral prophylactic cancer vaccine show tumor-specificity and immunotherapeutic potential.
abstract: MUC1 is a shared tumor antigen expressed on >80% of human cancers. We completed the first prophylactic cancer vaccine clinical trial based on a non-viral antigen, MUC1, in healthy individuals at-risk for colon cancer. This trial provided a unique source of potentially effective and safe immunotherapeutic drugs, fully-human antibodies affinity-matured in a healthy host to a tumor antigen. We purified, cloned, and characterized 13 IgGs specific for several tumor-associated MUC1 epitopes with a wide range of binding affinities. These antibodies bind hypoglycosylated MUC1 on human cancer cell lines and tumor tissues but show no reactivity against fully-glycosylated MUC1 on normal cells and tissues. We found that several antibodies activate complement-mediated cytotoxicity and that T cells carrying chimeric antigen receptors with the antibody variable regions kill MUC1(+) target cells, express activation markers, and produce interferon gamma. Fully-human and tumor-specific, these antibodies are candidates for further testing and development as immunotherapeutic drugs.
authors.affiliation: University of Pittsburgh School of Medicine, Department of Immunology, Pittsburgh, PA, USA.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Lohmueller
authors.affiliation: Cell Signaling Technology, Inc., Danvers, Massachusetts, USA.
authors.forename: Shuji
authors.initials: S
authors.lastname: Sato
authors.affiliation: Cell Signaling Technology, Inc., Danvers, Massachusetts, USA.
authors.forename: Lana
authors.initials: L
authors.lastname: Popova
authors.affiliation: Cell Signaling Technology, Inc., Danvers, Massachusetts, USA.
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Chu
authors.affiliation: Cell Signaling Technology, Inc., Danvers, Massachusetts, USA.
authors.forename: Meghan A
authors.initials: MA
authors.lastname: Tucker
authors.affiliation: Cell Signaling Technology, Inc., Danvers, Massachusetts, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Barberena
authors.affiliation: Cell Signaling Technology, Inc., Danvers, Massachusetts, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Innocenti
authors.affiliation: Florida Atlantic University, Department of Chemistry and Biochemistry, Boca Raton, Florida, USA.
authors.forename: Mare
authors.initials: M
authors.lastname: Cudic
authors.affiliation: University of Pittsburgh School of Medicine, Department of Immunology, Pittsburgh, PA, USA.|Carnegie Mellon University, Department of Biomedical Engineering, Pittsburgh, PAUSA.
authors.forename: James D
authors.initials: JD
authors.lastname: Ham
authors.affiliation: Cell Signaling Technology, Inc., Danvers, Massachusetts, USA.
authors.forename: Wan Cheung
authors.initials: WC
authors.lastname: Cheung
authors.affiliation: Cell Signaling Technology, Inc., Danvers, Massachusetts, USA.
authors.forename: Roberto D
authors.initials: RD
authors.lastname: Polakiewicz
authors.affiliation: University of Pittsburgh School of Medicine, Department of Immunology, Pittsburgh, PA, USA.
authors.forename: Olivera J
authors.initials: OJ
authors.lastname: Finn
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000906:Antibodies / Q000276:immunology*; D000915:Antibody Affinity / Q000276:immunology; D001483:Base Sequence; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D002460:Cell Line; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D061986:MCF-7 Cells; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D000906:Antibodies; D019496:Cancer Vaccines; D000939:Epitopes; D007074:Immunoglobulin G; D018396:Mucin-1; D007371:Interferon-gamma