A fully human anti-c-Kit monoclonal antibody 2G4 inhibits proliferation and degranulation of human mast cells.
Mol Cell Biochem
; 478(4): 861-873, 2023 Apr.
Article
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| MEDLINE
| ID: mdl-36107283
ABSTRACT
Given that mast cells are pivotal contributors to allergic diseases, various allergy treatments have been developed to inhibit them. 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-macrophage colony-stimulating factor, vascular endothelial growth factor, C-C 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Trastornos de la Activación de los Mastocitos
/
Hipersensibilidad
Límite:
Humans
Idioma:
En
Revista:
Mol Cell Biochem
Año:
2023
Tipo del documento:
Article