CN-122005780-A - Application of neutralizing antibody targeting macrophages in preparation of medicines for treating atopic dermatitis

Abstract

The application provides application of a neutralizing antibody targeting macrophages in preparation of a medicament for treating Atopic Dermatitis (AD), and relates to the technical field of biomedicine. The core is that by applying a neutralizing antibody capable of specifically recognizing and binding to a critical target of macrophage surface-colony stimulating factor 1 receptor (CSF 1R), the CSF1/CSF1R signal path is blocked, so that the macrophages driving AD pathological process are eliminated. The present application provides significant and versatile benefits in treating Atopic Dermatitis (AD) by administering neutralizing antibodies targeting a critical target of macrophages. The effects are verified in an MC 903-induced AD mouse model, and are particularly embodied in relieving core symptoms of diseases, intervening in key pathological links and improving the whole health condition, thereby laying a foundation for clinically treating atopic dermatitis.

Inventors

• BAI XUEQIANG
• ZHANG ZHIJUN
• ZHU YUBO
• ZHANG ZIMO
• ZHAO RUIQI

Assignees

• 南通大学

Dates

Publication Date

20260512

Application Date

20260202

Claims (9)

1. 1. The application of the neutralizing antibody of the targeting macrophage in preparing a medicament for treating atopic dermatitis is characterized in that the neutralizing antibody is a neutralizing antibody of a colony stimulating factor 1 receptor.
2. 2. The use of a neutralizing antibody targeting macrophages in the preparation of a medicament for the treatment of atopic dermatitis according to claim 1, characterized in that said αcsf1R eliminates macrophages driving the pathological course of AD by blocking CSF1/CSF1R signaling pathway.
3. 3. A medicament for treating atopic dermatitis, characterized in that the medicament comprises a neutralizing antibody of colony stimulating factor 1 receptor.
4. 4. A pharmaceutical composition according to claim 3, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable adjuvant.
5. 5. A pharmaceutical composition according to claim 3, wherein the pharmaceutical composition is in the form of at least one of an injection, an external preparation or a tablet.
6. 6. A pharmaceutical composition according to claim 5, wherein said injectable formulation comprises intraperitoneal injection, subcutaneous injection, or intravenous injection.
7. 7. A pharmaceutical composition according to claim 5, wherein the external preparation comprises cream, gel, lotion.
8. 8. A medicament according to claim 3, wherein the medicament is capable of alleviating core symptoms of atopic dermatitis, including reducing the number of itchy scratches, slowing down skin thickening, reducing clinical dermatitis scores.
9. 9. A pharmaceutical composition according to claim 3, wherein the pharmaceutical composition is capable of down-regulating the mRNA expression levels of IL-1 beta, TNF-alpha, IL-23, IL-33 in skin tissue.

Description

Application of neutralizing antibody targeting macrophages in preparation of medicines for treating atopic dermatitis Technical Field The application relates to the technical field of biomedicine, in particular to application of a neutralizing antibody targeting macrophages in preparation of a medicament for treating atopic dermatitis. Background Atopic dermatitis (Atopic Dermatitis, AD) is a common chronic, recurrent, inflammatory skin disease characterized by severe itching, skin barrier dysfunction and abnormal immune response. The pathogenesis of AD is complex, and involves many factors such as inheritance, environmental and skin barrier defects, immune disorders, and the like. For a long time, research has focused on the role of type 2 helper T cells (Th 2) and their cytokines produced (e.g., IL-4, IL-13, IL-31) as well as mast cells/basophils. Biological agents (such as dupu Li Youshan antibody, qu Luolu monoclonal antibody and the like) aiming at the targets have obvious curative effects in clinic, and the core position of a type 2 immune pathway in AD is proved. However, existing therapies still have limitations in that some patients either do not respond adequately (primary or secondary), or have adverse effects. This suggests that there is a more complex cellular network and immune redundancy in the pathogenesis of AD. In recent years, the key role of innate immune cells, particularly skin resident and recruited macrophages, in the initiation, chronicity and perception of itch of AD has been increasingly appreciated, providing a new target for developing new therapeutic strategies. There is a complex network of antigen presenting cells in the skin including langerhans cells, dendritic cells and resident inflammatory macrophages. Macrophages have extremely high plasticity and can be differentiated into different functional subtypes according to microenvironment signals. In the acute phase of AD, classical activated (M1-like) and alternative activated (M2-like) macrophages mediating type 2 inflammation are the dominant. They amplify local inflammatory responses by producing large amounts of pro-inflammatory factors (e.g., TNF- α, IL-1 β, IL-6) and chemokines, recruiting more immune cells (e.g., th2 cells, eosinophils). In the chronic phase of AD, the macrophage phenotype is further transformed into subtypes with stronger tissue remodelling and fibrosis functions, involved in skin thickening (lichenification) and barrier repair. Although the core role of macrophages in AD has been primarily revealed, no specific antibody drug specifically designed to target and regulate macrophage function at the lesion site of skin, in particular, its key pathogenic cytokines or surface receptors, has been known in the current therapeutic approaches for AD. Disclosure of Invention The present invention provides a method for treating AD by depleting macrophages using neutralizing antibodies that target macrophages. The core is that a neutralizing antibody (called alpha CSF1R for short) capable of specifically recognizing and combining with a macrophage surface key target-colony stimulating factor 1 receptor (Colony Stimulating Factor receptor) is used for blocking the CSF1/CSF1R signal path, so that the macrophages driving AD pathological process are eliminated. The application provides application of a neutralizing antibody targeting macrophages in preparation of a medicament for treating atopic dermatitis, wherein the neutralizing antibody is a neutralizing antibody of colony stimulating factor 1 receptor. Preferably, the αcsf1R eliminates macrophages driving the pathological course of AD by blocking CSF1/CSF1R signaling pathways. The application also provides a medicament for treating atopic dermatitis, which comprises a neutralizing antibody of colony stimulating factor 1 receptor. Preferably, other pharmaceutically acceptable adjuvants are included in the medicament. Preferably, the dosage form of the medicine is at least one of injection, external preparation or tablet. Preferably, the injection comprises intraperitoneal injection, subcutaneous injection and intravenous injection. Preferably, the external preparation comprises cream, gel and lotion. Preferably, the medicament is capable of alleviating the core symptoms of atopic dermatitis, including reducing the number of itchy scratches, slowing down skin thickening, reducing clinical dermatitis scores. Preferably, the agent can down-regulate the mRNA expression levels of IL-1 beta, TNF-alpha, IL-23, IL-33 in skin tissue. Compared with the prior art, the application at least comprises the following beneficial effects: Treatment of Atopic Dermatitis (AD) by administration of neutralizing antibodies targeting a critical target of macrophages (αcsf 1R) produces significant and versatile beneficial technical effects. The effects are systematically verified in an MC 903-induced AD mouse model, are particularly embodied in relieving core symptoms of diseases, inter