Pharmaceutical preparation of Anti-human CCR8 monoclonal antibody and use thereof

Abstract

Provided are a stable pharmaceutical preparation of an anti-human CCR8 monoclonal antibody and the use thereof. The pharmaceutical preparation of the anti-human CCR8 antibody is very stable, can still meet the requirements for pharmaceutical use after enduring long-term storage, high temperatures or low temperatures, freeze-thaw cycles and oscillation, and has wide application prospects.

Description

Anti-human CCR8 monoclonal antibody pharmaceutical preparation and its use Technical Field

[0001] The present disclosure belongs to the field of antibody preparations, and specifically relates to an anti-human CCR8 monoclonal antibody pharmaceutical preparation and its use. Technical Background

[0002] Immune checkpoint inhibitors, such as PD-1 / PD-L1, have shown promising results in the treatment of various tumors. However, their efficacy remains relatively low, ranging from approximately 15% to 40%, depending on the type of cancer. Furthermore, some patients who initially demonstrate clinical responses develop resistance over time, likely due to compensatory mechanisms in the tumor microenvironment (TME) that evade the antitumor effects of immune checkpoint inhibitors.

[0003] Treg cells are a lineage of CD4+ T cells that specifically express forkhead box P3 (Foxp3). Depending on their origin, they can be divided into naive, effector, and non-Treg cells. Naive Treg cells possess weak immunosuppressive functions. After stimulation with the T cell receptor (TCR), they proliferate and differentiate into effector Treg cells. Effector Treg cells are in a terminally differentiated immune state and possess strong immunosuppressive effects. They exert immunosuppression primarily through the release of inhibitory cytokines, direct killing of antigen-presenting cells, immune checkpoint inhibition, and metabolic regulation, such as the adenosine pathway. Non-Treg cells do not possess immunosuppressive activity but produce inflammatory cytokines. Generally, the number of effector Treg cells in human peripheral blood ranges from 1% to 5%, while in the TME, it is approximately 10% to 50%. Existing studies have shown that a high proportion of Treg infiltration in the TME is negatively correlated with survival across various tumor types. Therefore, targeted Treg depletion to activate tumor immune responses is expected to enhance tumor immunity.

[0004] Classic Treg-related targets such as CD25, CTLA4, and CCR4 have been shown to inhibit tumor growth by eliminating Tregs. However, these targets are also highly expressed on T effector cells, which can easily lead to adverse reactions. Therefore, identifying targets that are specifically expressed on tumor Tregs but have low or no expression on T effector cells for further development is an unmet clinical need.

[0005] The CC chemokine receptor 8 protein (CCR8) is a member of the chemokine receptor subfamily and a G protein-coupled receptor. Its ligands include CCL1. The primary function of CCR8 is to participate in the recruitment of Treg and Th2 cells to inflammatory and tumor sites. CCR8 target expression is highly specific. Studies have shown that CCR8 expression is low in Treg cells, CD4+ T cells, and CD8+ T cells in the peripheral blood of cancer patients, while it is highly upregulated in Treg cells in the corresponding patient tumor tissues, and low in CD4+ and CD8+ T cells in tumor tissues. Other literature has compared CCR8 expression in different tissues of normal mice and tumor model mice. The results showed that CCR8 expression is very low or essentially absent in normal mouse tissues, but highly expressed in tumor tissues of tumor-bearing mice, with low expression in the spleen and lymph nodes and essentially absent in other tissues. In summary, antibodies targeting CCR8 can specifically eliminate Tregs in tumor tissues and alleviate the immunosuppression of tumor tissues. It is expected to have a synergistic effect when used in combination with PD-1 / PD-L1 drugs, without affecting tumor-infiltrating T effector cells, resulting in a lower risk of systemic autoimmunity and better safety.

[0006] Public content

[0007] In order to pursue better clinical effects, the present invention first obtained an anti-human CCR8 monoclonal antibody, named J06.

[0008] Following the development of the J06 antibody, extensive research and development of a formulation for the J06 antibody was conducted, ultimately resulting in a solution formulation optimized for the J06 monoclonal antibody and capable of stably preserving the antibody. This formulation effectively prevents aggregation, degradation, oxidation, or denaturation of the J06 monoclonal antibody protein, thereby maintaining the biological activity of its active ingredients and making it suitable for clinical use. Furthermore, based on the J06 monoclonal antibody formulation, in-depth research into its pharmacological properties was conducted, revealing that it exhibits excellent anti-tumor activity.

[0009] Public details

[0010] 1. Terminology

[0011] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

[0012] Before describing the present disclosure in detail below, it should be understood that the present disclosure is not limited to the specific methodologies, protocols and reagents described herein, as these may vary. It should also be understood that the terms used herein are only for the purpose of describing specific embodiments and are not intended to limit the scope of the present disclosure. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art to which the present disclosure belongs.

[0013] Certain embodiments disclosed herein include numerical ranges, and certain aspects of the present disclosure may be described in terms of ranges. Unless otherwise stated, it should be understood that numerical ranges or descriptions in terms of ranges are intended for simplicity and convenience and should not be considered as strict limitations on the scope of the present disclosure. Therefore, descriptions in terms of ranges should be considered to specifically disclose all possible subranges and all possible specific numerical points within the range, as these subranges and numerical points have been clearly stated herein. Regardless of the width of the numerical value, the above principles apply equally. When describing in terms of ranges, the range includes the endpoints of the range.

[0014] When referring to a measurable value such as an amount, a temporal duration, etc., the term "about" is meant to include variations of ±20%, or in some cases ±10%, or in some cases ±5%, or in some cases ±1%, or in some cases ±0.1% of the specified value.

[0015] The term "antibody," as used herein, typically refers to a Y-shaped tetrameric protein comprising two heavy (H) polypeptide chains and two light (L) polypeptide chains held together by covalent disulfide bonds and non-covalent interactions. Natural IgG antibodies have this structure. Each light chain comprises a light chain variable domain (VL) and a light chain constant domain (CL). Each heavy chain comprises a heavy chain variable domain (VH) and a heavy chain constant domain (CH) (or heavy chain constant region (CH)).

[0016] The term "monoclonal antibody" (or "mAb") refers to a substantially homogeneous antibody produced by a single cell clone that is directed against a specific antigenic epitope. Monoclonal antibodies can be prepared using a variety of techniques known in the art, including hybridoma technology, recombinant technology, phage display technology, transgenic animals, synthetic technology, or a combination of these techniques.

[0017] 2. Public Content

[0018] The present disclosure aims to provide a stable monoclonal antibody preparation suitable for anti-human CCR8 and its use.

[0019] The present disclosure provides a technical solution: a pharmaceutical preparation of an anti-human CCR8 monoclonal antibody, comprising an anti-human CCR8 monoclonal antibody or an antigen-binding fragment thereof and a buffer, wherein the three CDR sequences in the heavy chain variable region of the anti-human CCR8 monoclonal antibody or the antigen-binding fragment thereof are SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively; and the three CDR sequences in the light chain variable region are SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively; and the buffer is a sodium acetate buffer, a histidine buffer, or a sodium citrate buffer.

[0020] Preferably, the sequence of the heavy chain variable region of the anti-human CCR8 monoclonal antibody or antigen-binding fragment thereof is shown in SEQ ID NO: 7, and the sequence of the light chain variable region is shown in SEQ ID NO: 8.

[0021] Preferably, the heavy chain sequence of the anti-human CCR8 monoclonal antibody or antigen-binding fragment thereof is shown in SEQ ID NO: 9, and the light chain sequence is shown in SEQ ID NO: 10. Preferably, the formulation further comprises a stabilizer selected from sucrose, trehalose, or sorbitol.

[0022] Preferably, the preparation further comprises a solubilizer, and the solubilizer is selected from polysorbate 20, polysorbate 80 or poloxamer 188.

[0023] Preferably, the pH value of the preparation is 4.5-6.0.

[0024] Preferably, the content of the anti-human CCR8 monoclonal antibody or its antigen-binding fragment in the preparation is 20-160 mg / ml, preferably, its content is 20 mg / ml, 50 mg / ml, 80 mg / ml, 100 mg / ml, 120 mg / ml or 160 mg / ml.

[0025] Preferably, the content of sodium acetate in the preparation is 5 to 20 mmol / L, preferably, its content is 5 mmol / L, 10 mmol / L, 15 mmol / L or 20 mmol / L.

[0026] Preferably, the content of sucrose in the preparation is 50-90 mg / ml, preferably, the content is 50 mg / ml, 70 mg / ml, 80 mg / ml or 90 mg / ml.

[0027] Preferably, the content of polysorbate 80 in the preparation is 0.04-2 mg / ml, preferably, its content is 0.04 mg / ml, 0.2 mg / ml, 0.5 mg / ml, 0.7 mg / ml or 2 mg / ml.

[0028] Preferably, the content of polysorbate 20 in the preparation is 0.5-2 mg / ml, preferably, the content is 0.5 mg / ml, 0.7 mg / ml or 2 mg / ml.

[0029] Preferably, the preparation comprises 20-160 mg / ml of anti-human CCR8 monoclonal antibody or antigen-binding fragment thereof, 5-20 mmol / L of sodium acetate, 50-90 mg / ml of sucrose, and 0.5-2 mg / ml of polysorbate 20, and the pH value of the preparation is 4.5-6.0.

[0030] Preferably, the preparation comprises 20-160 mg / ml of anti-human CCR8 monoclonal antibody or antigen-binding fragment thereof, 5-20 mmol / L of sodium acetate, 50-90 mg / ml of sucrose, and 0.04-2 mg / ml of polysorbate 80, and the pH value of the preparation is 4.5-6.0.

[0031] Preferably, the preparation comprises 20-30 mg / ml of anti-human CCR8 monoclonal antibody or antigen-binding fragment thereof, 10 mmol / L of sodium acetate, 90 mg / ml of sucrose, and 0.5 mg / ml of polysorbate 20, and the pH value of the preparation is 4.5-6.0.

[0032] Preferably, the preparation comprises 20-30 mg / ml of anti-human CCR8 monoclonal antibody or antigen-binding fragment thereof, 10 mmol / L of sodium acetate, 90 mg / ml of sucrose, and 0.5 mg / ml of polysorbate 80, and the pH value of the preparation is 4.5-6.0.

[0033] Another technical solution provided by the present disclosure is: a freeze-dried preparation, which is obtained by freeze-drying the above-mentioned pharmaceutical preparation.

[0034] Another technical solution provided by the present disclosure is: use of the above-mentioned pharmaceutical preparation or the above-mentioned lyophilized preparation in the preparation of a drug for treating advanced solid tumors.

[0035] The preparations disclosed herein have the following beneficial effects:

[0036] The preparation disclosed herein is very stable and can still meet pharmaceutical use requirements after long-term storage, high or low temperature, freeze-thaw cycles, and oscillation, and has broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 is a graph of monomer purity in the pH range screening test using SE-HPLC.

[0038] Figure 2 is a graph showing the main peak purity of nrCE-SDS in the pH range screening test.

[0039] Figure 3 is the SE-HPLC monomer purity diagram of the excipient screening test.

[0040] Figure 4 is the nrCE-SDS main peak purity diagram of the excipient screening test. DETAILED DESCRIPTION

[0041] The present disclosure is further described in detail by the following examples. Based on the present disclosure, changes in the concentrations of the formulation components or the addition of other substances, which do not significantly affect the stability of the anti-human CCR8 antibody, are still considered part of the present disclosure.

[0042] Size Exclusion Chromatography (SE-HPLC)

[0043] Size exclusion chromatography was used to determine the content of high molecular weight substances (HMWS), monomers and low molecular weight substances (LMWS) in this product. This method uses X Bridge BEH SEC columns (Waters) were used and run on a Waters e2695-2489 HPLC system (Waters). Detection was at 215 nm; the mobile phase consisted of 100 mM sodium phosphate, 250 mM sodium chloride buffer, pH 7.3; the flow rate was 0.5 ml / min, and the run time was 30 min. The sample was diluted with the mobile phase to a protein content of 1 mg / ml, and 20 μg was injected. Integration was performed using Empower 3 software (Waters).

[0044] Capillary electrophoresis (CE-SDS)

[0045] The main peak and (LC+HC) purity were determined by non-reducing CE-SDS (nrCE) and reducing CE-SDS (rCE), respectively. This determination was performed on a SCIEX PA800 plus capillary electrophoresis system using 50 μm ID non-coated quartz capillaries with an effective capillary separation length of 20 cm (total length 30.2 cm) and a PDA 220 nm bandwidth of 10 nm.

[0046] Surface Plasmon Resonance technology (SPR)

[0047] The affinity of this product for recombinant human CCR8 was determined using surface plasmon resonance (SPR) technology. This method utilizes direct immobilization. Recombinant human CCR8 protein was first immobilized on the experimental channel of a CM5 chip via amino coupling, with a coupling capacity of approximately 15 RU. A 1 nM concentration of this product was serially diluted to 31.25 pM in running buffer. A series of concentrations, ranging from 1 nM to 31.25 pM, was then passed through the reference channel and experimental channel, with binding for 3 minutes and dissociation for 10 minutes. Each cycle was followed by regeneration with 50 mM HCl for 30 seconds, repeated twice. Data were analyzed using Biacore 8K Evaluation software, fitted using a 1:1 binding model.

[0048] The following specific embodiments are listed to illustrate the present disclosure. It should be understood that these examples are only for illustrating the present disclosure, rather than limiting the scope of the present disclosure.

[0049] Example 1 Acquisition and sequence information of anti-human CCR8 monoclonal antibody J06

[0050] According to the contents described in PCT / US2023 / 060686, the anti-human CCR8 monoclonal antibody J06 (corresponding to anti-CCR8 Mab1187 in the patent) was obtained. The three CDR sequences in the heavy chain variable region of the anti-human CCR8 monoclonal antibody J06 are: SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively; the three CDR sequences in the light chain variable region are: SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. The sequence of the heavy chain variable region is shown in SEQ ID NO: 7, and the sequence of the light chain variable region is shown in SEQ ID NO: 8. The sequence of the heavy chain is shown in SEQ ID NO: 9, and the sequence of the light chain is shown in SEQ ID NO: 10.

[0051] Example 2 Preparation of anti-human CCR8 monoclonal antibody J06

[0052] J06, an anti-human CCR8 monoclonal antibody, is expressed in CHO cells. The complete monoclonal antibody is composed of two heavy chains (HC) and two light chains (LC), each consisting of 453 amino acid residues and 219 amino acid residues. J06 was expressed in CHO cells and purified to obtain a stock solution for further testing.

[0053] Example 3 Solubilizer Screening Test

[0054] The protein used in the following experiments was the anti-human CCR8 monoclonal antibody J06 prepared in Example 2. Based on a recipe of 30 mg / ml protein, 90 mg / ml sucrose, and a 10 mmol / L sodium acetate buffer system, the type and dosage of solubilizers (polysorbate 20 and polysorbate 80) were screened. The formulation is shown in Table 1:

[0055] Table 1 Solubilizer screening test prescription

[0056] The prepared samples were tested for influencing factors according to the prescription table: under high temperature conditions (40℃±2℃), sampling and testing were carried out at 0 days, 1 week, 2 weeks, and 3 weeks respectively; under oscillation conditions, sampling and testing were carried out at 24 hours and 48 hours respectively; under freeze-thaw conditions (freezing at -80℃ for 16 hours and thawing at 25℃ for 8 hours as one cycle), sampling and testing were carried out after 6 and 10 times.

[0057] Inspection items: appearance, presence of visible foreign matter, protein content, size exclusion chromatography (SE-HPLC) purity, and non-reducing capillary electrophoresis (nrCE-SDS) purity.

[0058] The test results are shown in Table 2:

[0059] Table 2 Solubilizer screening test results

[0060] Note: NA means the test was not performed.

[0061] Test results showed that after three weeks of storage at high temperature (40°C ± 2°C), the sample without solubilizer (R0) and the sample with 0.2 mg / ml polysorbate 20 (R1) exhibited visible protein flocculent material. The main peak purity of samples (R1-R4) containing different solubilizer types (polysorbate 20, polysorbate 80) and concentrations (0.2 mg / ml, 0.5 mg / ml) all showed a consistent downward trend. When tested under oscillation for 48 hours and under freeze-thaw conditions for 10 cycles, no significant changes in any of the test parameters were observed between formulations R1-R4. Based on these test results, 0.5 mg / ml polysorbate 20 and either 0.2 mg / ml or 0.5 mg / ml polysorbate 80 are suitable as solubilizers for J06.

[0062] Example 4 pH range screening test

[0063] Based on the recipe of 20 mg / ml protein, 90 mg / ml sucrose, 0.5 mg / ml polysorbate 80, and 10 mmol / L sodium acetate buffer, the pH range was screened. The pH range was designed to be 4.0-6.0, and the recipe is shown in Table 3:

[0064] Table 3 pH value screening test prescription table

[0065] Prepare the liquid according to the prescription, sterilize and filter it before packaging. The prepared samples were tested for influencing factors (high temperature 40℃±2℃), and samples were taken for testing at 0 days, 1 week, and 2 weeks.

[0066] Test items: appearance, protein content, presence of visible foreign matter, size exclusion chromatography purity (SE-HPLC), non-reducing capillary electrophoresis purity (nrCE-SDS). Test results are shown in Table 4:

[0067] Table 4 pH value screening test results

[0068] Note: NA means the test was not performed.

[0069] The test results showed that after two weeks of exposure to high temperature (40°C ± 2°C), no significant changes were observed in the appearance, presence of visible foreign matter, or protein content of each formulation. As shown in Figures 1 and 2, compared to time zero, the SE-HPLC and nrCE-SDS purities of the pH 4.0 sample (R1) decreased significantly by 4.3% and 2.7%, respectively. The purity parameters of formulations R6 to R11 (pH 4.5 to 6.0) decreased slightly, but the downward trend was generally consistent, with no significant differences between the formulations. Based on the test results of each formulation, the candidate pH range was determined to be 4.5 to 6.0.

[0070] Example 5 Excipient Screening Test

[0071] The protein used in the following experiments is the anti-human CCR8 monoclonal antibody J06 prepared in Example 2. A variety of excipients were used for formulation screening, and the formulation design is shown in Table 5:

[0072] Table 5 Excipient screening test prescription

[0073] According to the prescription table, the prepared samples were subjected to the influencing factor test (high temperature 40℃±2℃), and samples were taken for testing on the 0th day, the 7th day, the 14th day, and the 30th day respectively;

[0074] Test items: appearance, presence of visible foreign matter, protein content, size exclusion chromatography (SE-HPLC) purity, and non-reducing capillary electrophoresis (nrCE-SDS) purity. The test results are shown in Table 6:

[0075] Table 6 Excipient screening test results

[0076] The test results showed that after 30 days of high temperature (40°C ± 2°C) exposure, the appearance, presence of visible foreign matter, and protein content of each formulation remained unchanged compared to the initial exposure. All purity test indicators showed a slight downward trend, with the downward trend being generally consistent. After 30 days of high temperature (40°C ± 2°C), no significant differences were observed in any of the test indicators across the formulations. Based on these test results, the protein concentration can be selected from 20 to 160 mg / ml, sodium acetate, histidine, and sodium citrate can all be used as buffers, sucrose, trehalose, and sorbitol can all be used as stabilizers, and polysorbate 80 and poloxamer 188 can both be used as solubilizers.

[0077] Conclusion: Through the above preparation prescription screening test, the buffer system can be selected from sodium acetate, histidine, and sodium citrate buffer systems, the stabilizer can be selected from sucrose, trehalose, and sorbitol, and the solubilizer can be selected from polysorbate 20, polysorbate 80, and poloxamer 188.

[0078] Example 6 Preparation stability test

[0079] Based on the above test results, the following preferred formulation was selected for stability study: protein concentration 20 mg / ml, sucrose as stabilizer, concentration 90 mg / ml; polysorbate 80 as solubilizer, concentration 0.5 mg / ml; sodium acetate buffer as buffer system, concentration 10 mmol / L, pH range 4.5-6.0. It includes: forced condition test (high temperature test), accelerated test, and long-term test. The sample placement method in the stability study was upright; the samples for long-term, accelerated, and high-temperature tests were all carried out in simulated market packaging. The various test conditions are shown in Table 7:

[0080] Table 7 Stability test conditions of each preparation

[0081] The stability results under the above-mentioned investigation conditions are shown in Tables 8 to 10:

[0082] Table 8 Accelerated test results

[0083] Table 9 High temperature test results

[0084] Table 10 Long-term test results

[0085] The above results prove that the antibody preparation is relatively stable and can still meet the quality standards after being tested at high temperature of 40℃±2℃ and accelerated temperature of 25℃±2℃.

[0086] Example 7 Affinity Analysis of Anti-Human CCR8 Monoclonal Antibody J06 Preparation and Human CCR8 Recombinant Protein

[0087] Based on the above results, affinity analysis was performed on the preferred preparation in Example 6. The affinity of the anti-human CCR8 monoclonal antibody J06 preparation to recombinant human CCR8 protein was determined using SPR technology. The results are shown in Table 11. The affinity analysis fitted K of J06 preparation to recombinant human CCR8 D The value is 7.77 pM, indicating that the J06 preparation has a high affinity for recombinant human CCR8.

[0088] Table 11 Kinetic fitting results of affinity analysis of J06 preparation for recombinant human CCR8

Claims

1. A pharmaceutical preparation of a monoclonal antibody against human CCR8, characterized in that: The invention comprises an anti-human CCR8 monoclonal antibody or an antigen-binding fragment thereof and a buffer, wherein the three CDR sequences in the heavy chain variable region of the anti-human CCR8 monoclonal antibody or the antigen-binding fragment thereof are: SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:3, respectively; the three CDR sequences in the light chain variable region of the anti-human CCR8 monoclonal antibody or the antigen-binding fragment thereof are: SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6, respectively; and the buffer is a sodium acetate buffer, a histidine buffer or a sodium citrate buffer.

2. The pharmaceutical preparation according to claim 1, characterized in that The sequence of the heavy chain variable region of the anti-human CCR8 monoclonal antibody or its antigen-binding fragment is shown in SEQ ID NO:7, and the sequence of the light chain variable region is shown in SEQ ID NO:

8.

3. The pharmaceutical preparation according to claim 2, characterized in that The heavy chain sequence of the anti-human CCR8 monoclonal antibody or the antigen-binding fragment thereof is shown in SEQ ID NO:9, and the light chain sequence is shown in SEQ ID NO:

10.

4. The pharmaceutical preparation according to claim 1, characterized in that The preparation further comprises a stabilizer, which is selected from sucrose, trehalose or sorbitol.

5. The pharmaceutical preparation according to claim 1, characterized in that The preparation further comprises a solubilizer, which is selected from polysorbate 20, polysorbate 80 or poloxamer 188.

6. The pharmaceutical preparation according to claim 1, characterized in that The pH value of the preparation is 4.5-6.

0.

7. The pharmaceutical preparation according to claim 1, characterized in that The content of the anti-human CCR8 monoclonal antibody or its antigen-binding fragment in the preparation is 20-160 mg / ml, preferably, the content is 20 mg / ml, 50 mg / ml, 80 mg / ml, 100 mg / ml, 120 mg / ml or 160 mg / ml.

8. The pharmaceutical preparation according to claim 1, characterized in that The content of sodium acetate in the preparation is 5-20 mmol / L, preferably, the content is 5 mmol / L, 10 mmol / L, 15 mmol / L or 20 mmol / L.

9. The pharmaceutical preparation according to claim 4, characterized in that The content of sucrose in the preparation is 50-90 mg / ml, preferably, the content is 50 mg / ml, 70 mg / ml, 80 mg / ml or 90 mg / ml.

10. The pharmaceutical preparation according to claim 5, characterized in that The content of polysorbate 80 in the preparation is 0.04-2 mg / ml, preferably, the content is 0.04 mg / ml, 0.2 mg / ml, 0.5 mg / ml, 0.7 mg / ml or 2 mg / ml.

11. The pharmaceutical preparation according to claim 5, characterized in that The content of polysorbate 20 in the preparation is 0.5-2 mg / ml, preferably, the content is 0.5 mg / ml, 0.7 mg / ml or 2 mg / ml.

12. The pharmaceutical preparation according to any one of claims 1 to 11, characterized in that The preparation comprises 20-160 mg / ml of anti-human CCR8 monoclonal antibody or antigen-binding fragment thereof, 5-20 mmol / L of sodium acetate, 50-90 mg / ml of sucrose, and 0.5-2 mg / ml of polysorbate 20, and the pH value of the preparation is 4.5-6.

0.

13. The pharmaceutical preparation according to any one of claims 1 to 11, characterized in that The preparation comprises 20-160 mg / ml of anti-human CCR8 monoclonal antibody or antigen-binding fragment thereof, 5-20 mmol / L of sodium acetate, 50-90 mg / ml of sucrose, and 0.04-2 mg / ml of polysorbate 80, and the pH value of the preparation is 4.5-6.

0.

14. The pharmaceutical preparation according to claim 12, characterized in that The preparation contains 20-30 mg / ml of anti-human CCR8 monoclonal antibody or antigen-binding fragment thereof, 10 mmol / L of sodium acetate, 90 mg / ml of sucrose, and 0.5 mg / ml of polysorbate 20, and the pH value of the preparation is 4.5-6.

0.

15. The pharmaceutical preparation according to claim 13, characterized in that The preparation comprises 20-30 mg / ml of anti-human CCR8 monoclonal antibody or antigen-binding fragment thereof, 10 mmol / L of sodium acetate, 90 mg / ml of sucrose, and 0.5 mg / ml of polysorbate 80, and the pH value of the preparation is 4.5-6.

0.

16. A lyophilized preparation obtained by freeze-drying the pharmaceutical preparation according to any one of claims 1 to 15.

17. Use of the pharmaceutical preparation according to any one of claims 1 to 15 or the lyophilized preparation according to claim 16 in the preparation of a medicament for treating advanced solid tumors.

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