title: Generation of new peptide-Fc fusion proteins that mediate antibody-dependent cellular cytotoxicity against different types of cancer cells.
abstract: Antibody-dependent cellular cytotoxicity (ADCC), a key effector function for the clinical effectiveness of monoclonal antibodies, is triggered by the engagement of the antibody Fc domain with the Fcγ receptors expressed by innate immune cells such as natural killer (NK) cells and macrophages. Here, we fused cancer cell-binding peptides to the Fc domain of human IgG1 to engineer novel peptide-Fc fusion proteins with ADCC activity. The designed fusion proteins were expressed in human embryonic kidney 293T cells, followed by purification and characterization by western blots. One of the engineered variants (WN-Fc), bound with high affinity to a wide range of solid tumor cell lines (e.g., colon, lung, prostate, skin, ovarian, and mammary tumors). Treatment of cancer cells with the engineered peptide-Fc fusions in the presence of effector NK cells potentially enhanced cytotoxicity, degranulation, and interferon-γ production by NK cells when compared to cells treated with the Fc control. The presence of competing peptides inhibited NK cell activation. Furthermore, a bispecific peptide-Fc fusion protein activated NK cells against HER-1- and/or HER-2-expressing cancer cells. Collectively, the engineered peptide-Fc fusions constitute a new promising strategy to recruit and activate NK cells against tumor cells, a primary goal of cancer immunotherapy.
authors.affiliation: Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital , Montebello, Oslo, Norway.
authors.forename: Mouldy
authors.initials: M
authors.lastname: Sioud
authors.affiliation: Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital , Montebello, Oslo, Norway.
authors.forename: Phuong
authors.initials: P
authors.lastname: Westby
authors.affiliation: Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital , Montebello, Oslo, Norway.
authors.forename: Julie Kristine E
authors.initials: JK
authors.lastname: Olsen
authors.affiliation: Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital , Montebello, Oslo, Norway.
authors.forename: Anne
authors.initials: A
authors.lastname: Mobergslien