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Omalizumab, an anti-immunoglobulin E antibody, is a representative therapy that can alleviate allergy symptoms by inhibiting mast cell degranulation. However, omalizumab cannot reduce the proliferation and accumulation of mast cells, which is a fundamental cause of allergic diseases. c-Kit is essential for the proliferation, survival, and differentiation of mast cells. Excessive c-Kit activation triggers various mast cell diseases, such as asthma, chronic spontaneous urticaria, and mastocytosis. Herein, we generated 2G4, an anti-c-Kit antibody, to develop a therapeutic agent for mast cell diseases. The therapeutic efficacy of 2G4 antibody was evaluated in LAD2, a human mast cell line. 2G4 antibody completely inhibited c-Kit signaling by blocking the binding of stem cell factor, known as the c-Kit ligand. Inhibition of c-Kit signaling led to the suppression of proliferation, migration, and degranulation in LAD2 cells. Moreover, 2G4 antibody suppressed the secretion of pro-inflammatory cytokines, including granulocyte\u2013macrophage colony-stimulating factor, vascular endothelial growth factor, C\u2013C motif chemokine ligand 2, brain-derived neurotrophic factor, and complement component C5\/C5a, which can exacerbate allergy symptoms. Taken together, these results suggest that 2G4 antibody has potential as a novel therapeutic agent for mast cell diseases.<\/jats:p>","DOI":"10.1007\/s11010-022-04557-3","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T10:02:47Z","timestamp":1663236167000},"page":"861-873","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A fully human anti-c-Kit monoclonal antibody 2G4 inhibits proliferation and degranulation of human mast cells"],"prefix":"10.1007","volume":"478","author":[{"given":"Kwang-Hyeok","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Ock","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Gyu","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,9,15]]},"reference":[{"key":"4557_CR1","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1006\/cyto.2001.0907","volume":"15","author":"VC Broudy","year":"2001","unstructured":"Broudy VC, Lin NL, Sabath DF (2001) The fifth immunoglobulin-like domain of the Kit receptor is required for proteolytic cleavage from the cell surface. 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