Binding molecules targeting ccl5 and their use in combination in the treatment of th2-type inflammation related diseases

Abstract

The application belongs to the technical field of biological medicine, and particularly relates to a binding molecule targeting CCL5 and application of the binding molecule in combination with drugs in treatment of Th2-type inflammation related diseases. The application discloses use of a binding molecule targeting CCL5 or a pharmaceutical composition comprising the binding molecule in preparation of a product having one or more of the following functions: 1) prevention and / or treatment of Th2-type inflammation related diseases; 2) reduction of skin lesion tissue thickness; 3) reduction of clinical score of atopic dermatitis; 4) reduction of scratching behavior; 5) reduction of tissue damage; 6) alleviation of inflammatory reaction and inhibition of expression of inflammatory factors; and 7) reduction of inflammatory cell infiltration. The binding molecule targeting CCL5 or the pharmaceutical composition comprising the binding molecule has important value in prevention and treatment of immune inflammatory diseases such as atopic dermatitis, allergic rhinitis, asthma, food allergy or drug allergy.

Description

Technical Field

[0001] This application relates to the field of biomedical technology, and in particular to the application of CCL5-targeting binding molecules and their combination therapy in the treatment of Th2-type inflammatory diseases. Background Technology

[0002] Atopic dermatitis (AD) is a common, chronic, relapsing inflammatory skin disease, mainly characterized by pruritus, erythema, exudation, crusting, and thickening of the skin. Its pathogenesis is complex, involving skin barrier dysfunction, abnormal immune regulation, and the abnormal expression of various inflammatory factors and chemokines. Among these, the inflammatory pathway dominated by the Th2 immune response plays a crucial role in the occurrence and development of atopic dermatitis.

[0003] Atopic dermatitis is an allergic disease. Current understanding of its immunological pathogenesis includes Th2 immune bias and chemokine-mediated immune cell recruitment. Clinically, treatment for atopic dermatitis primarily relies on topical or systemic corticosteroids, calcineurin inhibitors, small molecule immunomodulators, and targeted biologics targeting pathways such as IL-4Rα. While these treatments can alleviate symptoms to some extent, they generally suffer from unstable efficacy, high relapse rates, and limited safety with long-term use, necessitating the development of new therapeutic targets and combination therapy strategies.

[0004] Chemokine CCL5 (CC motif chemokine ligand 5) is involved in the recruitment and activation of various immune cells (including T lymphocytes, eosinophils, and myeloid immune cells) in inflammatory responses and has been shown to play an important role in a variety of immune-related diseases. However, a systemic technical approach targeting CCL5 for the treatment of atopic dermatitis has not yet been established, and its synergistic effects with existing treatments or other targeted factors lack clear technical guidance. Summary of the Invention

[0005] To address the aforementioned technical problems, this application provides the use of a CCL5-targeting binding molecule or a pharmaceutical composition including a CCL5-targeting binding molecule in the preparation of a product having one or more of the following functions: 1) Prevention and / or treatment of Th2-type inflammatory diseases; 2) Reduce the thickness of the lesion tissue; 3) Reduce clinical scores for atopic dermatitis; 4) Reduce scratching behavior; 5) Reduce tissue damage; 6) Alleviates inflammatory response and inhibits the expression of inflammatory factors; 7) Reduce inflammatory cell infiltration.

[0006] This application also provides a pharmaceutical composition comprising a CCL5-targeting binding molecule used in the above-described applications and a pharmaceutically acceptable carrier or excipient.

[0007] The purpose of this invention is to provide a new therapeutic use for allergic diseases, specifically including: 1. To provide the use of CCL5-targeting binding molecules for the treatment of atopic dermatitis; 2. To provide the use of the aforementioned CCL5-targeting binding molecule in combination with existing atopic dermatitis drugs to improve therapeutic efficacy; 3. To provide the combined use of the aforementioned CCL5-targeting binding molecule and the TSLP-targeting binding molecule to further enhance the therapeutic effect on Th2-type inflammatory diseases (including AD).

[0008] The technical solution of this invention: In one aspect, the use of a CCL5-targeting binding molecule in the preparation of a medicament for the treatment of atopic dermatitis is provided.

[0009] Secondly, based on the above-mentioned uses, the CCL5-targeting binding molecule is provided for use in combination with at least one atopic dermatitis drug to prepare a drug for treating atopic dermatitis.

[0010] Thirdly, in a further embodiment, the CCL5-targeting binding molecule is provided in combination with the TSLP-targeting binding molecule for the preparation of a pharmaceutical composition for treating atopic dermatitis.

[0011] The beneficial effects of this application include, but are not limited to: (1) the CCL5-targeting molecule alone can significantly alleviate the Th2-type inflammatory response associated with atopic dermatitis; (2) the CCL5-targeting molecule can produce synergistic or additive therapeutic effects with existing AD treatment drugs; (3) when the CCL5-targeting molecule is used in combination with the TSLP-targeting binding molecule, it shows better effects in improving skin lesions and inhibiting the expression of Th2-related inflammatory factors; (4) this invention provides new technical ideas and application approaches for the long-term treatment and combination therapy of allergic diseases. Attached Figure Description

[0012] This application will be further described by way of exemplary embodiments, which will be described in detail with reference to the accompanying drawings. These embodiments are not limiting, wherein: Figure 1The results show the signs and behavioral assessments of anti-CCL5 monoclonal antibody alone or in combination with anti-TSLP monoclonal antibody in the treatment of MC903-induced atopic dermatitis in mice. Figure 1 a shows the ear appearance of mice in each group after the modeling process was completed; Figure 1 b shows that compared with the Isotype Ab group, the Anti-CCL5 Ab group, the Anti-TSLP Ab group, or the Dual Ab group all significantly reduced the lesion thickness. Figure 1 c shows that, compared with the Isotype Ab group, the Anti-CCL5 Ab group, the Anti-TSLP Ab group, or the Dual Ab group all significantly reduced AD scores; Figure 1 The results show that, compared with the Isotype Ab group, the Anti-CCL5 Ab group, the Anti-TSLP Ab group, or the Dual Ab group all significantly reduced scratching behavior.

[0013] Figure 2 The results show the effects of anti-CCL5 monoclonal antibody alone or in combination with anti-TSLP monoclonal antibody on MC903-induced histological changes in skin lesions. Figure 2 a shows the HE staining results of ear skin lesions in each group of mice after the modeling process was completed; Figure 2 b shows the thickness of the ear tissue epidermis in each group of mice after the modeling process was completed; Figure 2 c represents the dermal thickness of the ear tissue in each group of mice after the modeling process was completed. Figure 2 d shows the inflammatory cell infiltration status of the ear tissue of mice in each group after the modeling process.

[0014] Figure 3 The results show the effects of anti-CCL5 monoclonal antibody alone or in combination with anti-TSLP monoclonal antibody on the expression of Th2-related inflammatory factors in MC903-induced skin lesions. Figure 3 a shows the relative expression level of the inflammatory factor IL-4 mRNA; Figure 3 b shows the relative expression level of the inflammatory factor IL-5 mRNA; Figure 3 c shows the relative expression level of the inflammatory factor IL-9 mRNA; Figure 3 d shows the relative expression level of the inflammatory factor IL-13 mRNA. Detailed Implementation

[0015] To more clearly illustrate the technical solutions of the embodiments in this specification, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are merely some examples or embodiments of this specification. For those skilled in the art, these drawings can be applied to other similar scenarios without creative effort. Unless obvious from the context or otherwise specified, the same reference numerals in the drawings represent the same structures or operations.

[0016] As indicated in this specification and claims, unless the context clearly indicates otherwise, the words "a," "an," "an," and / or "the" do not specifically refer to the singular and may also include the plural. Generally speaking, the terms "comprising" and "including" only indicate the inclusion of expressly identified steps and elements, which do not constitute an exclusive list, and the method or apparatus may also include other steps or elements.

[0017] Flowcharts are used in this specification to illustrate the operations performed by the system according to embodiments of this specification. It should be understood that the preceding or following operations are not necessarily performed in exact order. Instead, the steps can be processed in reverse order or simultaneously. Furthermore, other operations can be added to these processes, or one or more steps can be removed from them.

[0018] This application provides the use of a CCL5-targeting binding molecule or a pharmaceutical composition including a CCL5-targeting binding molecule in the preparation of a product having one or more of the following functions: 1) Prevention and / or treatment of Th2-type inflammatory diseases; 2) Reduce the thickness of the lesion tissue; 3) Reduce clinical scores for atopic dermatitis; 4) Reduce scratching behavior; 5) Reduce tissue damage; 6) Alleviates inflammatory response and inhibits the expression of inflammatory factors; 7) Reduce inflammatory cell infiltration.

[0019] Inflammation is the body's defensive response to stimuli, clinically manifested as redness, swelling, heat, pain, and functional impairment. It is classified into infectious and non-infectious types, and by course, into acute and chronic inflammation. Its pathological processes include tissue degeneration, fluid exudation, and cell proliferation, often accompanied by vasodilation and the release of inflammatory mediators. While inflammation is usually a beneficial biological defense response, it can damage the body's own tissues or trigger harmful reactions in specific sites (such as hyaline tissue). Systemic reactions can include fever and leukocytosis.

[0020] Th2-type inflammation is an immune response mediated by Th2 cells, primarily associated with allergic diseases and chronic inflammation. Its core mechanism involves the release of cytokines such as IL-4, IL-5, and IL-13, leading to elevated IgE antibodies and increased eosinophils, causing symptoms such as tissue redness, swelling, and itching. It is commonly seen in diseases such as asthma, atopic dermatitis, and allergic rhinitis.

[0021] The term "prevention and / or treatment" (and its grammatical variations) refers to an attempt to alter the natural course of disease in an individual being treated, and can be a clinical intervention performed for prevention or during the course of clinicopathological processes. The desired effects of treatment include, but are not limited to, preventing the onset or recurrence of disease, relieving symptoms, reducing any direct or indirect pathological consequences of the disease, preventing metastasis, slowing the rate of disease progression, improving or alleviating the disease state, and eliminating or improving prognosis.

[0022] In some embodiments, the Th2-type inflammation-related disease may include any one or more of atopic dermatitis, allergic rhinitis, asthma, food allergy, or drug allergy.

[0023] Allergic rhinitis, also known as hay fever, is a multifactorial disease caused by both genetic and environmental factors. This condition is characterized by an overreaction of the body's immune system to environmental allergens, such as pollen and dust mites, leading to chronic inflammation of the mucous membranes. Symptoms primarily include episodic sneezing, runny nose, and nasal congestion. Genetic factors, as well as environmental allergens such as fungal spores, dust mites, animal excrement, and certain foods, can all trigger allergic rhinitis. Common symptoms of allergic rhinitis include nasal itching, paroxysmal sneezing, clear nasal discharge, and nasal congestion, and symptoms can occur seasonally or intermittently throughout the year. In some cases, such as after exposure to allergens, patients may also experience eye symptoms such as itchy eyes, tearing, red and swollen eyes, and burning sensations, as well as respiratory symptoms such as itchy throat, chest tightness, cough, and asthma attacks.

[0024] Asthma is a common chronic inflammatory airway disease characterized by recurrent episodes of wheezing, shortness of breath, chest tightness, or coughing. In severe cases, it can lead to difficulty breathing and hypoxemia, often occurring or worsening at night and in the early morning. The onset of asthma is related to both genetic and environmental factors. Genetic factors primarily determine a patient's predisposition, while environmental factors such as various allergens, air quality, smoking, and exercise are specific triggers. Common types of asthma include exercise-induced, drug-induced, occupational, and allergic asthma.

[0025] Food allergy is an abnormal reaction mediated by the immune mechanism after the body ingests certain foods, and it can recur after exposure to the same food allergen. Food allergies are mainly classified into immunoglobulin (IgE)-mediated, non-IgE-mediated, and mixed-mediated hypersensitivity reactions. Food allergy is a systemic disease, divided into adult and childhood food allergies. Due to individual differences, the severity and location of symptoms vary. Symptoms include reactions in multiple systems such as the skin, respiratory tract, and gastrointestinal tract; in severe cases, anaphylactic shock can occur. Most reactions are caused by foods such as milk, eggs, and peanuts. In China, common allergenic foods include shrimp, mango, and shellfish.

[0026] Drug allergy is a specific adverse reaction to a drug in sensitized patients, belonging to the allergic reaction type of adverse drug reactions. Its mechanism involves the drug or its metabolites acting as antigens, triggering a specific antibody response or a sensitized lymphocyte response, leading to tissue damage or physiological dysfunction. This reaction occurs only in a small number of people with allergic constitutions. The first exposure may have a latent period before onset, while subsequent exposure may result in immediate symptoms. Clinical manifestations are diverse according to immunophenotyping: Type I may present with rash, angioedema, and anaphylactic shock; Type II presents with anemia, thrombocytopenia, and other hematological abnormalities; Type III causes fever, joint swelling and pain, and kidney damage; Type IV presents with delayed reactions such as fixed drug eruptions.

[0027] In some embodiments, the CCL5-targeting binding molecule can reduce the thickness of the epidermis and dermis in the damaged tissue.

[0028] In some embodiments, the inflammatory cells may be T lymphocytes. In some embodiments, preferably, the inflammatory cells may be helper T cells. In some embodiments, more preferably, the inflammatory cells may be Th2 cells.

[0029] In some embodiments, the CCL5-targeting binding molecule can alleviate tissue damage in atopic dermatitis.

[0030] In some embodiments, the CCL5-targeting binding molecule can reduce scratching behavior in atopic dermatitis tissue.

[0031] In some embodiments, the inflammatory response may be a Th2-type inflammatory response, preferably a Th2-type inflammatory response associated with atopic dermatitis.

[0032] In some embodiments, the inflammatory factor may be a Th2-related inflammatory factor. In some embodiments, preferably, the inflammatory factor may include any one or more of IL-4, IL-5, IL-9, or IL-13.

[0033] In some embodiments, the CCL5-targeting binding molecule may be selected from any one or more of small molecule compounds, monoclonal antibodies, polyclonal antibodies, antibody fragments, nanobodies, fusion proteins, or their functional equivalents. In some embodiments, preferably, the CCL5-targeting binding molecule may be a monoclonal antibody. In some embodiments, more preferably, the CCL5-targeting binding molecule may be an anti-CCL5 monoclonal antibody. In some embodiments, even more preferably, the CCL5-targeting binding molecule may be an anti-CCL5 neutralizing antibody.

[0034] Monoclonal antibodies are highly homogeneous antibodies produced from a single B cell clone, targeting only a specific antigenic epitope. Produced through hybridoma technology or genetic engineering methods, they are characterized by structural homogeneity and strong targeting, and are widely used in disease treatment, diagnosis, and scientific research.

[0035] Polyclonal antibodies are antibodies produced by multiple B cell clones that can bind to different epitopes and have different types of immunoglobulins.

[0036] Antibody fragments are small molecular portions that retain specific functions (especially antigen-binding ability) derived from intact antibodies (such as immunoglobulin G and IgG) through enzymatic digestion or genetic engineering.

[0037] Nanobodies are single-domain antibody fragments derived from camels that are naturally missing light chains. While their molecular weight is only 1 / 10 that of traditional antibodies, they possess unique advantages such as high stability and strong tissue penetration.

[0038] Fusion proteins are artificially synthesized single polypeptide chains produced by linking two or more originally independent gene coding sequences together through genetic engineering.

[0039] Neutralizing antibodies are soluble proteins secreted by adaptive immune response cells. They specifically bind to antigens on the surface of pathogenic microorganisms, preventing pathogens from invading cells and neutralizing their infectivity by blocking the binding of pathogens to host cell receptors. After a virus invades the human body, immune cells secrete neutralizing proteins into the bloodstream. These proteins bind to viral particles in the blood, preventing the virus from infecting cells and destroying the viral particles.

[0040] In some embodiments, the binding molecule targeting CCL5 may be selected from any one or more of humanized antibodies, fully human antibodies, or Fc-engineered antibodies.

[0041] In some embodiments, the pharmaceutical composition may further include any one or more of the following: a TSLP-targeting binding molecule, a glucocorticoid, a calcineurin inhibitor, a small molecule immunomodulator, or a biological agent.

[0042] In some embodiments, the TSLP-targeting binding molecule may be an antibody. Preferably, in some embodiments, the TSLP-targeting binding molecule may be a monoclonal antibody. More preferably, in some embodiments, the TSLP-targeting binding molecule may be an anti-TSLP monoclonal antibody. Further preferably, in some embodiments, the TSLP-targeting binding molecule may be an anti-TSLP neutralizing antibody.

[0043] This application also provides a pharmaceutical composition comprising a CCL5-targeting binding molecule used in the above-described applications and a pharmaceutically acceptable carrier or excipient.

[0044] The term “pharmaceutically acceptable” as used in this article generally means a compound, material, composition, and / or dosage form that is suitable, within reasonable medical judgment, for contact with human and animal tissues, organs, and / or body fluids without excessive toxicity, irritation, allergic response, or other problems or complications, in proportion to a reasonable benefit / risk ratio.

[0045] The excipients include various excipients and diluents, which are not essential active ingredients and do not cause adverse reactions after application. The excipients contain sterile water or physiological saline, stabilizers, excipients, antioxidants (ascorbic acid, etc.), buffers (phosphate, citric acid, other organic acids, etc.), preservatives, surfactants (PEG, Tween, etc.), chelating agents (EDTA, etc.), or binders. The excipients also contain other low molecular weight peptides, serum albumin, glycine, glutamine, asparagine, arginine, polysaccharides, monosaccharides, mannitol, or sorbitol. The aqueous solution of the excipients for injection is selected from physiological saline, glucose isotonic solution, D-sorbitol isotonic solution, D-mannose isotonic solution, D-mannitol or sugar alcohol isotonic solution. The aqueous solution for injection contains a solubilizer. The solubilizer is selected from alcohols (ethanol), polyols (propylene glycol or PEG), and / or nonionic surfactants (Tween 80 or HCO-50).

[0046] In the pharmaceutical composition provided in this application, the binding molecule targeting CCL5 can be a single active ingredient, or it can be combined with one or more other active components that are useful for the treatment of the disease to form a combined formulation.

[0047] The content of the active ingredient in the pharmaceutical composition is a safe and effective amount, which is understood by those skilled in the art. In general, it should be adjustable; for example, the dosage of the active ingredient in the pharmaceutical composition depends on the patient's weight, the type of application, the condition and severity of the disease.

[0048] In some embodiments, the pharmaceutical composition may further include any one or more of the following: a TSLP-targeting binding molecule, a glucocorticoid, a calcineurin inhibitor, a small molecule immunomodulator, or a biologic.

[0049] In some embodiments, the TSLP-targeting binding molecule may be an antibody. Preferably, in some embodiments, the TSLP-targeting binding molecule may be a monoclonal antibody. More preferably, in some embodiments, the TSLP-targeting binding molecule may be an anti-TSLP monoclonal antibody. Further preferably, in some embodiments, the TSLP-targeting binding molecule may be an anti-TSLP neutralizing antibody.

[0050] A method for preventing and / or treating Th2-type inflammation-related diseases, the method comprising administering to an individual with a Th2-type inflammation-related disease a therapeutically effective amount of a CCL5-targeting binding molecule, product, or pharmaceutical composition as described above.

[0051] The term "effective amount" refers to the quantity or dose of a formulation of the medicament or pharmaceutical composition of this application that, when administered to a patient in a single or multiple doses, produces the intended effect in the treated patient. An effective amount can be determined by a physician skilled in the art by considering a variety of factors, such as: the species of the mammal; its size, age, and general health; the specific disease involved; the degree or severity of the disease; the individual patient's response; the specific formulation administered; the mode of administration; the bioavailability characteristics of the administered formulation; the chosen dosing regimen; and the use of any concomitant therapies.

[0052] In some embodiments, the pharmaceutical composition may be a fixed-dose composition or a non-fixed-dose composition.

[0053] In some embodiments, the components of the pharmaceutical composition may be administered simultaneously, sequentially, or in a sequential manner.

[0054] In some embodiments, the pharmaceutical composition or its components are suitable for administration by injection, inhalation, topical application, or a combination thereof.

[0055] Unless otherwise specified, the experimental methods used in the following examples are conventional methods. Unless otherwise specified, the experimental materials used in the following examples were all purchased from conventional biochemical reagent companies. All quantitative experiments in the following examples were performed in triplicate, and the results were averaged.

[0056] Example 1 Therapeutic effect of anti-CCL5 monoclonal antibody in MC903-induced mouse AD model (a) Laboratory animals and grouping Female C57BL / 6 mice aged 6–8 weeks were randomly divided into the following experimental groups: Vehicle group, MC903+Vehicle group, MC903+Isotype Ab group, MC903+Anti-CCL5 Ab group, MC903+Anti-TSLP Ab group, MC903+Dual Ab group, and MC903+Steroid positive control group.

[0057] (II) AD Model Establishment Atopic dermatitis-like lesions in mice were induced by topical application of MC903 (calcipotriol). MC903 was dissolved in anhydrous ethanol to prepare a 10 mM stock solution and stored at –20°C protected from light. Before use, it was diluted 100 times with anhydrous ethanol and applied evenly to the ventral and dorsal sides of the ears of mice, 10 μL on each side, for 14 consecutive days. The vehicle group received only an equal volume of anhydrous ethanol topically.

[0058] (III) Dosing regimen All antibodies were administered via intraperitoneal injection, once every 3 days from the start of model initiation. The Anti-CCL5 group was given Anti-CCL5 Ab (Biolegend, 947003, anti-mouse CCL5 neutralizing antibody) 200 μg / mouse each time, and isotype control antibody (Biolegend, 400565) 200 μg / mouse each time; The Anti-TSLP group was given Anti-TSLP Ab (Biolegend, 515202, anti-mouse TSLP neutralizing antibody) 200 μg / mouse each time, and isotype control antibody 200 μg / mouse each time; The Dual Ab group was given 200 μg of each of the two neutralizing antibodies per animal; The Isotype Ab group was given 400 μg / animal of isotype control antibody.

[0059] The Steroid positive control group received topical application of 0.1% mometasone furoate ointment once daily during the modeling period.

[0060] (iv) Testing Indicators After modeling, the appearance of skin lesions was recorded and ear thickness was measured. The atopic dermatitis index (ADI) was used for semi-quantitative assessment across four dimensions: erythema / congestion, edema / thickening, scaling / dryness, and excoriation / erosion. Each dimension was scored from 0 to 3 based on severity: 0 for no significant change; 1 for mild (focal or small area, mild symptoms); 2 for moderate (expanded area or significant symptoms); and 3 for severe (widespread involvement, significant symptoms with significant exudation / crusting or severe excoriation). The four scores were summed to obtain the total ADI score, ranging from 0 to 12, with higher scores indicating more severe skin lesions. Furthermore, scratching behavior in mice was counted. Figure 1 Subsequently, skin lesion tissue was taken for HE staining, and the thickness of the epidermis and dermis was measured, and the infiltration of inflammatory cells (T cells) was statistically analyzed. Figure 2 RNA was extracted from skin lesions, and the relative expression levels of inflammatory cytokine mRNAs such as IL-4, IL-5, IL-9, and IL-13 were detected by qPCR. Figure 3 ).

[0061] (V) Experimental Results The results showed that topical MC903 could stably induce typical AD-like skin lesions in mice. Compared with the Isotype Ab group, treatment with Anti-CCL5 Ab or Anti-TSLP Ab significantly reduced lesion thickness, AD scores, and scratching behavior; the DualAb group showed the most significant improvement. Histological and molecular tests further indicated that the combined treatment was more effective in reducing histological damage and inhibiting the expression of Th2-related inflammatory factors.

[0062] The basic concepts have been described above. Obviously, for those skilled in the art, the detailed disclosure above is merely illustrative and does not constitute a limitation of this specification. Although not explicitly stated herein, those skilled in the art may make various modifications, improvements, and corrections to this specification. Such modifications, improvements, and corrections are suggested in this specification and therefore remain within the spirit and scope of the exemplary embodiments described herein.

[0063] Furthermore, this specification uses specific terms to describe embodiments thereof. For example, "an embodiment," "one embodiment," and / or "some embodiments" refer to a particular feature, structure, or characteristic associated with at least one embodiment of this specification. Therefore, it should be emphasized and noted that references to "an embodiment," "one embodiment," or "an alternative embodiment" in different locations throughout this specification do not necessarily refer to the same embodiment. Moreover, certain features, structures, or characteristics in one or more embodiments of this specification can be appropriately combined.

[0064] In some embodiments, numbers describing the quantity of components and attributes are used. It should be understood that such numbers used in the description of embodiments are modified in some examples with the terms "approximately," "approximately," or "generally." Unless otherwise stated, "approximately," "approximately," or "generally" indicates that the numbers are allowed to vary by ±20%. Accordingly, in some embodiments, the numerical parameters used in the specification and claims are approximate values, which may be changed depending on the characteristics required by individual embodiments. In some embodiments, numerical parameters should take into account specified significant digits and employ a general method of digit reservation. Although the numerical ranges and parameters used to confirm their breadth of range in some embodiments of this specification are approximate values, in specific embodiments, such values ​​are set as precisely as feasible.

[0065] Finally, it should be understood that the embodiments described in this specification are merely illustrative of the principles of the embodiments described herein. Other variations may also fall within the scope of this specification. Therefore, alternative configurations of the embodiments described herein are intended to be illustrative rather than limiting, and should be considered consistent with the teachings of this specification. Accordingly, the embodiments described herein are not limited to those explicitly introduced and described herein.

Claims

1. Use of a CCL5-targeting binding molecule or a pharmaceutical composition comprising a CCL5-targeting binding molecule in the preparation of a product having one or more of the following functions: 1) Prevention and / or treatment of Th2-type inflammatory diseases; 2) Reduce the thickness of the lesion tissue; 3) Reduce clinical scores for atopic dermatitis; 4) Reduce scratching behavior; 5) Reduce tissue damage; 6) Alleviates inflammatory response and inhibits the expression of inflammatory factors; 7) Reduce inflammatory cell infiltration.

2. The use as described in claim 1, characterized in that, The Th2-type inflammatory diseases include any one or more of atopic dermatitis, allergic rhinitis, asthma, food allergy, or drug allergy; And / or, the CCL5-targeting binding molecules reduce the thickness of the epidermis and dermis in the lesion tissue; And / or, the inflammatory cells are T lymphocytes, preferably, the inflammatory cells are helper T cells, and more preferably, the inflammatory cells are Th2 cells; And / or, the CCL5-targeting binding molecules alleviate tissue damage in atopic dermatitis; And / or, the CCL5-targeting binding molecules reduce scratching behavior in atopic dermatitis tissue.

3. The use as described in claim 1, characterized in that, The inflammatory response is a Th2-type inflammatory response, preferably a Th2-type inflammatory response associated with atopic dermatitis; And / or, the inflammatory factor is a Th2-related inflammatory factor, preferably, the inflammatory factor includes any one or more of IL-4, IL-5, IL-9 or IL-13.

4. The use as described in claim 1, characterized in that, The CCL5-targeting binding molecule is selected from any one or more of small molecule compounds, monoclonal antibodies, polyclonal antibodies, antibody fragments, nanobodies, fusion proteins, or their functional equivalents. Preferably, the CCL5-targeting binding molecule is a monoclonal antibody; more preferably, the CCL5-targeting binding molecule is an anti-CCL5 monoclonal antibody; and even more preferably, the CCL5-targeting binding molecule is an anti-CCL5 neutralizing antibody.

5. The use as described in claim 1, characterized in that, The binding molecule targeting CCL5 is selected from any one or more of humanized antibodies, fully human antibodies, or Fc-engineered antibodies.

6. The use as described in claim 1, characterized in that, The pharmaceutical composition further includes any one or more of the following: a TSLP-targeting binding molecule, a glucocorticoid, a calcineurin inhibitor, a small molecule immunomodulator, or a biological agent.

7. The use as described in claim 6, characterized in that, The TSLP-targeting binding molecule is an antibody, preferably a monoclonal antibody, more preferably an anti-TSLP monoclonal antibody, and even more preferably an anti-TSLP neutralizing antibody.

8. A pharmaceutical composition comprising a CCL5-targeting binding molecule as described in any one of claims 1 to 7, and a pharmaceutically acceptable carrier or excipient.

9. The pharmaceutical composition according to claim 8, characterized in that, The pharmaceutical composition further includes any one or more of the following: a TSLP-targeting binding molecule, a glucocorticoid, a calcineurin inhibitor, a small molecule immunomodulator, or a biological agent.

10. The pharmaceutical composition according to claim 9, characterized in that, The TSLP-targeting binding molecule is an antibody, preferably a monoclonal antibody, more preferably an anti-TSLP monoclonal antibody, and even more preferably an anti-TSLP neutralizing antibody.

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