PHARMACEUTICAL COMPOSITION OF TGF-β RECEPTOR FUSION PROTEIN, AND ITS USE.

Abstract

This description outlines a pharmaceutical composition of a TGF-β receptor fusion protein and its use. Specifically, the pharmaceutical composition comprises a TGF-β receptor fusion protein in a sodium citrate buffer, and the TGF-β receptor fusion protein comprises a PD-L1 antibody-targeted portion and an extracellular TGF-βRII region. The pharmaceutical composition may also include a sugar and a nonionic surfactant.

Description

PHARMACEUTICAL COMPOSITION OF TGF-β RECEPTOR FUSION PROTEIN, AND ITS USE FIELD OF INVENTION The present description relates to the field of pharmaceutical preparations and, in particular, to a pharmaceutical composition comprising PD-L1 / TGF-pRII antibody extracellular region fusion protein and its use as a drug. BACKGROUND OF THE INVENTION The statements herein provide background information related to the present description and do not necessarily constitute the state of the art. During cancer treatment, people have recognized the high toxicity of chemotherapy, and chemotherapy can lead to the generation of drug-resistant cancer cells. Even with targeted therapies that specifically target overexpressed or overactivated proteins associated with tumor survival and growth, some cancer cells will still mimic the therapy's ability to reduce or evade its reliance on targeted pathways, and these cancer cells will survive through other means. Tumor immunotherapy has attracted considerable attention in recent years and is a focal point in the field of antitumor treatment. Its most significant advantage is the increased difficulty in generating drug resistance. Tumor immunotherapy primarily utilizes immunological principles and methods to enhance the immunogenicity of tumor cells and their susceptibility to destruction by effector cells, thereby stimulating and improving the body's antitumor immune response. Tumor immunotherapy involves infusing immune cells and effector molecules into a host, where these two components work together with the immune system to destroy tumors and inhibit tumor growth. Programmed cell death receptor 1 (PD-1) is a member of the CD28 superfamily. PD-1 is expressed on activated T lymphocytes, B lymphocytes, and myeloid cells. PD-1 has two hemispheres: programmed cell death ligand 1 (PD-L1) and PD-L2. PD-L1 interacts with the PD-1 receptor on T lymphocytes and plays a crucial role in the negative regulation of the immune response. PD-L1 protein expression can be detected in various human tumor tissues. The microenvironment at the tumor site can induce PD-L1 expression in tumor cells, and the expressed PD-L1, in turn, contributes to oncogenesis and tumor growth and induces apoptosis of antitumor T lymphocytes. Inhibitors of the PD-1 / PD-L1 pathway block the binding of PD-1 to PD-L1, suppressing negative regulatory signals, restoring T lymphocyte activity, and enhancing the immune response. Therefore, immunoregulation with PD-1 / PD-L1 as a specific target is of great importance for tumor suppression. QLncnn / Lznz / B / Yi Transforming growth factor-β (TGF-β) belongs to the TGF-β superfamily, which regulates cell growth and differentiation. TGF-β transmits signals through a heterotetrameric receptor complex, composed of two type I and two type II serine / threonine kinase transmembrane receptors. TGF-β is a multifunctional cytokine that exerts a tumor-suppressing or tumor-promoting effect in a cell-dependent or baseline-dependent manner. The tumor-suppressing effect of TGF-β depends on its ability to induce the expression of multiple genes. When mutations or epigenetic modifications are introduced during tumor development, cancer cells gradually become tolerant to the inhibitory effect of TGF-β, ultimately leading to tumor growth. Studies have found that blocking the TGF-β signaling pathway can reduce tumor metastasis. The metastatic capacity of tumor cells was found to be inhibited when the truncated Smad2 / 3 negative mutant inhibited the TGF-β signaling pathway in breast tumor cell lines. A study of colon cancer microsatellite instability found that the inactive TOG-βMI mutation reduced metastasis and increased the postoperative survival rate of patients. However, in general, the effect is weak when the TGF-β signaling pathway inhibitor is administered alone in clinical treatment, probably because TGF-β is primarily abnormally expressed in tumor cells, while it is difficult for the TGF-β signaling pathway inhibitor to target the tumor alone, resulting in low efficacy or low bioavailability of the inhibitor. Therefore, based on the targeting and neutralization of TGF-β in a tumor microenvironment, inhibition of the PD-1 / PD-L1 pathway can restore T lymphocyte activity, improve the immune response, and enhance the inhibitory effect on oncogenesis and development more effectively. A previous PCT application by the applicant, PCT / CN2016 / 104320 (publication number WO2017084495), provides a PD-L1 antibody. Currently, publications have been made on the antibody / TGF-β receptor fusion protein, such as in WO2006074451A2, WO2009152610A1, WO2011109789A2, WO2013164694A1, WO2014164427A1, WO2015077540A2, WO9309228A1, WO9409815A1, WO2015077540A2, WO2015118175A2, etc. Among them, Merck describes a bifunctional PD-L1 / TGF-β fusion protein, Bintrafusp Alfa (WO2015118175, also known as M7824, FP17022). Currently, Bintrafusp Alfa is in clinical trials for tumors such as gastric cancer, lung cancer, esophageal cancer, NSCLC, and biliary cancer. However, antibody drugs using the prior art technique become unstable due to their high molecular weights, complex structures, and susceptibility to degradation, polymerization, or the development of undesirable chemical modifications.In order to make the antibody suitable for administration, maintain stability during storage and subsequent use, and to exert a better effect, research on stable antibody drug preparations is particularly important. QLncnn / Lznz / B / Yi BRIEF DESCRIPTION OF THE INVENTION The present description provides a pharmaceutical composition comprising a PD-L1 / TGF-βHII fusion protein, which is more conducive to production and administration, and has more stable performance; the pharmaceutical composition comprises: - a TGF-β receptor fusion protein, and - a buffer, wherein the buffer is selected from the group consisting of a histidine salt buffer, a succinate buffer, a phosphate buffer, and a citrate buffer. In some formulations, the buffer is a citrate buffer. In some formulations, the histidine salt buffer is a histidine-hydrochloric acid buffer; and the succinate buffer is a succinic acid-sodium succinate buffer; the citrate buffer is a citric acid-sodium citrate buffer; in some formulations, the buffer is a citric acid-sodium citrate buffer. In an alternative modality, the concentration of the TGF-β receptor fusion protein in the above-described pharmaceutical composition is approximately 0.5 mg / mL to approximately 100 mg / mL, preferably approximately 30 mg / mL to approximately 70 mg / mL. In some formulations, the concentration of the TGF-β receptor fusion protein in the pharmaceutical composition ranges from 0.5 mg / mL to 100 mg / mL, preferably from 30 mg / mL to 70 mg / mL. Non-limiting examples of TGF-β receptor fusion protein concentrations include approximately 30 mg / mL, approximately 35 mg / mL, approximately 40 mg / mL, approximately 45 mg / mL, approximately 50 mg / mL, approximately 55 mg / mL, approximately 60 mg / mL, approximately 65 mg / mL, approximately 70 mg / mL, and preferably approximately 50 mg / mL. In some formulations, the concentration of the TGF-β receptor fusion protein in the pharmaceutical composition is 30 mg / mL, 35 mg / mL, 40 mg / mL, 45 mg / mL, 50 mg / mL, 55 mg / mL, 60 mg / mL, 65 mg / mL, 70 mg / mL, most preferably 50 mg / mL. In an alternative embodiment, the pH value of the buffer in the above-described pharmaceutical composition is approximately 5.0 to approximately 7.5, preferably approximately 6.0 to approximately 6.5, and optionally approximately 6.0, approximately 6.1, approximately 6.2, approximately 6.3, approximately 6.4, approximately 6.5, most preferably approximately 6.2. In some forms, the pH value of the buffer is 5.0 to 7.5, or 6.0 to 6.5, preferably 6.0, 6.1, 6.2, 6.3, 6.4 or 6.5, most preferably 6.2. In an alternative configuration, the damper concentration is from about 5mM to about 30mM, QLncnn / Lznz / E / Yi preferably from about 5mM to about 20mM; its non-limiting examples involve 5mM, 6mM, 7mM, 8mM, 9mM, 10mM, 12mM, 14mM, 16mM, 18mM, 20mM, more preferably 10mM. In some modalities, the buffer concentration is 5 mM to 30 mM, preferably 5 mM to 20 mM; and in some modalities, the buffer concentration is approximately 10 mM, approximately 12 mM, approximately 14 mM, approximately 16 mM, approximately 18 mM, approximately 20 mM, and more preferably approximately 10 mM. In an alternative embodiment, the pharmaceutical composition described above also comprises saccharide. The saccharide in this description comprises conventional compounds / compositions (CH₂O) not derived from them, including monosaccharides, disaccharides, trisaccharides, polysaccharides, sugar alcohols, reducing saccharides, non-reducing saccharides, and the like. In some embodiments, the saccharide is selected from the group consisting of: glucose, sucrose, trehalose, lactose, fructose, dextran, glycerol, erythritol, arabitol, xylitol, sorbitol, mannitol, melibiose, melezitose, melitriose, mannotriose, stachyose, maltose, lactulose, maltulose, sorbitol, maltitol, lactitol, isomaltulose, and so forth. The preferred saccharide is a non-reducing disaccharide, most preferably trehalose or sucrose and most preferably sucrose. In an alternative embodiment, the concentration of the saccharide in the above-described pharmaceutical composition is approximately 50 mg / mL to approximately 100 mg / mL, preferably approximately 60 mg / mL to approximately 90 mg / mL; non-limiting examples involve 60 mg / mL, 65 mg / mL, 70 mg / mL, 75 mg / mL, 80 mg / mL, 85 mg / mL, 90 mg / mL, most preferably 80 mg / mL. In some forms, the concentration of saccharide is 50 mg / mL to 100 mg / mL, preferably 60 mg / mL to 90 mg / mL; and in some forms, the concentration of saccharide is approximately 60 mg / mL, approximately 65 mg / mL, approximately 70 mg / mL, approximately 75 mg / mL, approximately 80 mg / mL, approximately 85 mg / mL or approximately 90 mg / mL. In an alternative embodiment, the above-described pharmaceutical composition further comprises a surfactant, which may be selected from the group consisting of polysorbate 20, polysorbate 80, polyhydroxyalkylene, Triton, sodium dodecylsulfonate, sodium laurylsulfonate, sodium octylglucoside, laurylsulfobetaine, myristylsulfobetaine, linoleylsulfobetaine, stearylsulfobetaine, laurylsarcosine, myristylsarcosine, linoleylsarcosine, stearylsarcosine, linoleylbetaine, myristylbetaine, cetylbetaine, laurel amidopropylbetaine, cocaamidopropylbetaine, linoleamidopropylbetaine, myristamidopropylbetaine, palmitamidopropylbetaine, isostearyl amidopropylbetaine, myristamidopropyl-dimethylamine, palmamidopropyl-dimethylamine, isostearamidopropyl-dimethylamine, sodium methyl coco, sodium methyloleurate, polyethylene glycol, polypropylene glycol, ethylene-propylene glycol copolymer, etc.The preferred surfactant is polysorbate 80 or polysorbate 20, more preferably polysorbate 80. QLncnn / Lznz / E / Yi In another alternative embodiment, the surfactant concentration in the pharmaceutical composition described above is approximately 0.1 mg / mL to approximately 0.8 mg / mL, more preferably approximately 0.4 mg / mL to approximately 0.8 mg / mL. In some embodiments, the surfactant concentration is 0.1 mg / mL to 0.8 mg / mL, preferably 0.4 mg / mL to 0.8 mg / mL, more preferably approximately 0.4 mg / mL, approximately 0.45 mg / mL, approximately 0.5 mg / mL, approximately 0.55 mg / mL, approximately 0.6 mg / mL, approximately 0.7 mg / mL, approximately 0.8 mg / mL. In some forms, the surfactant concentration is 0.4 mg / mL, 0.45 mg / mL, 0.5 mg / mL, 0.55 mg / mL, 0.6 mg / mL, 0.7 mg / mL or 0.8 mg / mL, more specifically 0.4 mg / mL. In an alternative embodiment, the pharmaceutical composition described above comprises: (a) approximately 0.5 mg / mL to approximately 100 mg / mL of TGF-β receptor fusion protein, (b) approximately 5 mM to approximately 30 mM of citrate buffer, (c) approximately 50 mg / mL to approximately 100 mg / mL of sucrose and (d) approximately 0.1 mg / mL to approximately 0.8 mg / mL of polysorbate 80, preferably the pH of the pharmaceutical composition is approximately 5.0 to approximately 7.5, more preferably approximately 6.0 to approximately 6.5. In an alternative embodiment, the pharmaceutical composition described above comprises: 0.5 mg / mL to 100 mg / mL of TGF-β receptor fusion protein, 5 mM to 30 mM citrate buffer, mg / mL to 100 mg / mL of sucrose, and O.lmg / mL 0.8mg / mL of polysorbate 80; Preferably, the pH of the pharmaceutical composition is 5.0 to 7.5, more preferably 6.0 to 6.5. In an alternative embodiment, the pharmaceutical composition described above comprises: (a) approximately 30 mg / mL to approximately 70 mg / mL of TGF-β receptor fusion protein, (b) approximately 5 mM to approximately 20 mM of citric acid and sodium citrate buffer, (c) approximately 60 mg / mL to approximately 90 mg / mL of sucrose and (d) approximately 0.4 mg / mL to approximately 0.8 mg / mL of polysorbate 80, preferably the pH of the pharmaceutical composition is approximately 6.0 to approximately 6.5. In an alternative embodiment, the pharmaceutical composition described above comprises: 30 mg / mL to 70 mg / mL of TGF-β receptor fusion protein, 20 mM to 20 mM of citric acid-sodium citrate buffer, and 90 mg / mL to 30 mg / mL of sucrose, and 0.4mg / mL to 0.8mg / mL of polysorbate 80; QLncnn / Lznz / E / Yi The pH of the pharmaceutical composition is approximately 6.0 to approximately 6.5. In an alternative embodiment, the pharmaceutical composition comprises: (a) approximately 50 mg / mL of TGF-β receptor fusion protein, (b) approximately 10 mM of citric acid and sodium citrate buffer, (c) approximately 80 mg / mL of sucrose and (d) approximately 0.4 mg / mL of polysorbate 80, the pH of the pharmaceutical composition is preferably approximately 6.2. In an alternative embodiment, the pharmaceutical composition comprises: 50mg / mL of TGF-β receptor fusion protein, mM of citric acid-sodium citrate buffer, mg / mL of sucrose, and 0.4mg / mL of polysorbate 80; Preferably, the pH of the pharmaceutical composition is approximately 6.2. In an alternative embodiment, the TGF-β receptor fusion protein in the pharmaceutical composition described above is shown as general formula (I): Ab-L-TGF^RII ECD (I) wherein the ECD of TGF^RII is a truncated form of an extracellular region of TGF^RII; Ab is a PD-L1 antibody or antigen-binding fragment thereof; L is a linking sequence. In an alternative embodiment, the linking sequence in the pharmaceutical composition described above is (G4S)xG, where x is an integer from 3 to 6. In an alternative embodiment, x has a value of 3, 4, 5, or 6, preferably 4. In an alternative embodiment, the truncated form of the extracellular region of TGF-βRII is an extracellular domain sequence of TGF-βRII (shown as SEQ ID NO: 14) with a deletion of up to 26 consecutive amino acid residues at the amino terminus (also called the N terminus). In some embodiments, the truncated form of the extracellular region of TGF-βKII is an extracellular domain sequence of TGF-βKII with a deletion of 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or 26 consecutive amino acid residues at the N terminus. In some embodiments, the TGF-βHII ECD sequence in the pharmaceutical composition described above is shown as SEQ ID NO: 14, 15, 16, or 17. Preferably, the sequence is shown as SEQ ID NO: 15. In an alternative embodiment, the PD-L1 antibody or antigen-binding fragment thereof in the pharmaceutical composition described above comprises: HCDR1, HCDR2 and HCDR3, shown as SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively; and LCDR1, LCDR2 and LCDR3 are shown as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6, QLncnn / Lznz / B / Yi respectively. In an alternative embodiment, the PD-L1 antibody or antigen-binding fragment thereof in the above-described pharmaceutical composition comprises: HCDR1, HCDR2 and HCDR3, which are shown as SEQ ID NO: 1, SEQ ID NO: 10 and SEQ ID NO: 3, respectively, and LCDR1, LCDR2 and LCDR3 are shown as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6, respectively. In an alternative embodiment, the PD-L1 antibody or antigen-binding fragment thereof in the above-described pharmaceutical composition comprises: a variable heavy chain region shown as SEQ ID NO:7 and a variable light chain region shown as SEQ ID NO:8; or, includes: a heavy chain variable region shown as SEQ ID NO:9 and a light chain variable region shown as SEQ ID NO: 11. In an alternative embodiment, the heavy chain amino acid sequence of the PD-L1 antibody in the above-described pharmaceutical composition is shown as SEQ ID NO: 12 or has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity with respect to the amino acid sequence shown as SEQ ID NO: 12; The light chain amino acid sequence of the PD-L1 antibody is shown as SEQ ID NO: 13 or has at least 85%, 86%, 87%, 88%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity with respect to the amino acid sequence shown as SEQ ID NO: 13. In an alternative embodiment of the above-described pharmaceutical composition, in the TGF-β receptor fusion protein, the ECD TGF-pRII is fused to the carboxyl end of the PD-L1 antibody heavy chain via a linking sequence. In some forms, the TGF-β receptor fusion protein comprises: • a fusion peptide formed by the PD-L1 antibody heavy chain fused to TOR-BIP ECD, the sequence of which is shown as SEQ ID NO:23 or has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity with the sequence shown as SEQ ID NO:23, and • the PD-L1 antibody light chain, the sequence of which is shown as SEQ ID NO: 13 or has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity with the sequence shown as SEQ ID NO: 13. In other forms, the TGF-β receptor fusion protein comprises: • a fusion peptide formed by the PD-L1 antibody heavy chain fused to TOR-βI QLncnn / Lznz / E / Yi ECD, whose sequence is shown as SEQ ID NO:24 or has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity with the sequence shown as SEQ ID NO:24, and • the PD-L1 antibody light chain, whose sequence is shown as SEQ ID NO: 13 or has at least 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity with the sequence shown as SEQ ID NO: 13. The present description also provides a method for preparing the above-described pharmaceutical composition, comprising a step of contacting the TGF-β receptor fusion protein with a buffer, e.g., performing buffer replacement in the TGF-β receptor fusion protein stock solution, and the buffer is preferably citrate buffer; more preferably citric acid and sodium citrate buffer, the concentration of the buffer being preferably from about 5 mM to about 20 mM; non-limiting examples involve 5 mM, 6 mM, 7 mM, 8 mM, 9 mM, 10 mM, 12 mM, 14 mM, 16 mM, 18 mM, 20 mM, more preferably 10 mM; the pH of the buffer is from about 6.0 to about 6.5, non-limiting examples involve 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, preferably 6.2.In an alternative embodiment, the buffer concentration is from 5 mM to 20 mM, non-limiting examples implying approximately 5 mM, approximately 6 mM, approximately 7 mM, approximately 8 mM, approximately 9 mM, approximately 10 mM, approximately 12 mM, approximately 14 mM, approximately 16 mM, approximately 18 mM, approximately 20 mM, more preferably approximately 10 mM; the pH of the buffer is from 6.0 to 6.5, non-limiting examples implying approximately 6.0, approximately 6.1, approximately 6.2, approximately 6.3, approximately 6.4, approximately 6.5, preferably approximately 6.2. The present description also provides a method for preparing the above-described pharmaceutical composition, further comprising the following steps after contacting the TGF-β receptor fusion protein with the buffer: adding sucrose and polysorbate 80 to the resulting solution (no order of precedence between the two), and then adjusting the volume with the buffer, wherein the concentration of the buffer solution is preferably from approximately 5mM to approximately 20mM, more preferably 5mM to 20mM, non-limiting examples imply 5mM, 8mM, 10mM, 12mM, 14mM, 16mM, 18mM, 20mM; the pH of the buffer is from approximately 6.0 to approximately 6.5, non-limiting examples imply 6.0, 6.1, 6.2, 6.3, 6.4, 6.5. The present description provides a method for preparing a lyophilized preparation comprising the TGF-β receptor fusion protein, comprising a lyophilization step of the above-described pharmaceutical composition. In an alternative modality, the method for preparing a lyophilized preparation described QLncnn / Lznz / B / Yi, formerly comprising the TGF-β receptor fusion protein, wherein lyophilization is carried out according to a method known in the art, such as, but not limited to, steps comprising pre-freezing, primary drying, and secondary drying. It is understood by those skilled that any method for removing water from the pharmaceutical composition described herein is applicable to this description. The present description provides a lyophilized preparation comprising the TGF-β receptor fusion protein, which is prepared by the method for preparing a lyophilized preparation described above. The present description provides a lyophilized preparation comprising the TGF-β receptor fusion protein, which can be reconstituted to form the above-described pharmaceutical composition. In some formulations, the lyophilized preparation may be stable at 2°C to 8°C for at least 3 months, at least 6 months, at least 12 months, at least 18 months, or at least 24 months. In some formulations, the lyophilized preparation may be stable at 40°C for at least 7 days, at least 14 days, or at least 28 days. The present description provides a reconstituted solution comprising the TGF-β receptor fusion protein, which is obtained by reconstituting the lyophilized preparation comprising the TGF-β receptor fusion protein described above. The present description also provides a method for preparing the reconstituted solution comprising the TGF-β receptor fusion protein described above, comprising: a reconstitution step of the lyophilized preparation described above, the solution used for reconstitution comprising, but not limited to, water for injection, physiological saline solution or glucose solution, preferably water for injection. This description also provides a manufactured item or kit comprising: the pharmaceutical composition according to this description; and the container(s). In some forms, the container is a glass bottle, such as, but not limited to, an injection bottle made from a neutral borosilicate glass vial. The present description also provides a manufactured article comprising containers comprising the pharmaceutical composition described above, or the lyophilized preparation thereof, or a reconstituted solution of the lyophilized preparation. This description also provides the use of any selected ingredient from the following for the preparation of a medicinal product: the pharmaceutical composition described above, or the lyophilized preparation, or the reconstituted solution of the lyophilized preparation, or the article of manufacture; the medicinal product is used to treat or QLncnn / Lznz / E / Yi inhibit diseases or disorders of proliferation or metastasis of tumor cells. In some cases, the disease or disorders are a tumor. In some modalities, the diseases or disorders are selected from the group consisting of: colorectal cancer, breast cancer, ovarian cancer, pancreatic cancer, gastric cancer, prostate cancer, kidney cancer, cervical cancer, myeloma, lymphoma, leukemia, thyroid cancer, endometrial cancer, uterine cancer, bladder cancer, neuroendocrine cancer, head and neck cancer, liver cancer, nasopharyngeal carcinoma, testicular cancer, lung cancer, small cell lung cancer, non-small cell lung cancer, melanoma, basal cell carcinoma, small cell carcinoma, dennatofibrosarcoma protuberans, Merkel cell carcinoma, glioblastoma, glioma, sarcoma, mesothelioma, and myelodysplastic syndrome. This description also provides a method for treating or inhibiting diseases or disorders related to the proliferation or metastasis of cancer cells, comprising providing a therapeutically effective amount of the above-described pharmaceutical composition, lyophilized preparation, reconstituted solution, or manufactured article to a subject in need. In some embodiments, the method comprises administering to the subject a unit dose of a composition comprising: 0.1 mg to 3000 mg of the TGF-β receptor fusion protein as described above, the pharmaceutical composition, lyophilized preparation, reconstituted solution, or manufactured article. In some embodiments, the disease or disorder(s) is a tumor.In some modalities, the diseases or disorders are selected from the group consisting of: colorectal cancer, breast cancer, ovarian cancer, pancreatic cancer, gastric cancer, prostate cancer, kidney cancer, cervical cancer, myeloma, lymphoma, leukemia, thyroid cancer, endometrial cancer, uterine cancer, bladder cancer, neuroendocrine cancer, head and neck cancer, liver cancer, nasopharyngeal carcinoma, testicular cancer, lung cancer, small cell lung cancer, non-small cell lung cancer, melanoma, basal cell carcinoma, small cell carcinoma, dennatofibrosarcoma protuberans, Merkel cell carcinoma, glioblastoma, glioma, sarcoma, mesothelioma, and myelodysplastic syndrome. The present invention also provides the TGF-β receptor fusion protein, pharmaceutical composition, lyophilized preparation, reconstituted solution, or article of manufacture described above, for treating or inhibiting diseases or disorders related to the proliferation or metastasis of cancer cells. In some modalities, the disease or disorder(s) is a tumor.In some modalities, diseases or disorders are selected from the group consisting of: colorectal cancer, breast cancer, ovarian cancer, pancreatic cancer, gastric cancer, prostate cancer, kidney cancer, cervical cancer, myeloma, lymphoma, leukemia, thyroid cancer, endometrial cancer, uterine cancer, bladder cancer, neuroendocrine cancer, head and neck cancer, liver cancer, nasopharyngeal carcinoma, testicular cancer, lung cancer, small cell lung cancer, non-small cell lung cancer, melanoma, basal cell carcinoma, small cell carcinoma, dermatofibrosarcoma protuberans, Merkel cell carcinoma, glioblastoma, glioma, sarcoma, mesothelioma, and myelodysplastic syndrome. As is widely known among experts in the field, one, some, or all of the characteristics of the various modalities described herein may be further combined to form other modalities of this description. The aforementioned modalities of this description and other modalities obtained by combination are further illustrated by the following detailed description. BRIEF DESCRIPTION OF THE FIGURES Figure 1 shows a schematic diagram depicting the structure of the fusion protein. Figure 2 shows results demonstrating the binding of fusion proteins to human TGF-βI in vitro. Figure 3 shows results demonstrating the binding of fusion proteins to human TGF-βI in vitro. Figure 4 shows results demonstrating the binding of fusion proteins to human PD-L1 in vitro. Figure 5 shows the result that demonstrates the detection of PD-1 / PD-L1 pathway blockade using in vitro fusion proteins. Figure 6 shows fusion proteins that inhibit TΘRβ-induced activity of the pSMAD3 flag in a dose-dependent manner. Figure 7 shows that all fusion protein samples enhance IFN-γ cytokine secretion by activated T lymphocytes. Figure 8 shows the effect of fusion proteins on tumor weight in mice having tumors. DETAILED DESCRIPTION OF THE INVENTION Terminology To facilitate understanding of the description, certain technical and scientific terms are specifically defined below. Unless otherwise defined herein, all other technical and scientific terms used herein have the meaning commonly understood by a person skilled in the field to which this description pertains. A buffer is a solution that tolerates changes in pH through the action of conjugate acid-base components. Examples of buffers that can control pH within a suitable range include acetate, succinate, gluconate, histidine, oxalate, lactate, phosphate, citrate, tartrate, fumarate, and glycylglycine. A histidine salt buffer is a buffer comprising histidine radical ions. Examples of histidine salt buffers include histidine hydrochloride, histidine acetate, histidine phosphate, histidine sulfate, and the like; preferably histidine hydrochloride buffer. The histidine-hydrochloride buffer is prepared from histidine and hydrochloric acid. A citrate buffer is a buffer comprising citrate radical ions. Examples of citrate buffers include citric acid-sodium citrate, citrate-potassium citrate, citrate-calcium citrate, citrate-magnesium citrate, and the like. The preferred citrate buffer is citric acid-sodium citrate. A succinate buffer is a buffer comprising succinate radical ions. Examples of succinate buffers include succinic acid-sodium succinate, succinic acid-potassium succinate, succinic acid-calcium succinate, and similar compounds. The preferred succinate buffer is succinic acid-sodium succinate. A phosphate buffer is a buffer comprising phosphate radical ions. Examples of phosphate buffers include disodium hydrogen phosphate-sodium monobasic phosphate, disodium hydrogen phosphate-potassium monobasic phosphate, and similar compounds. The preferred phosphate buffer is disodium hydrogen phosphate-sodium monobasic phosphate. An acetate buffer is a buffer comprising acetate radical ions. Examples of acetate buffers include acetic acid-sodium acetate, histidine acetate, acetic acid-potassium acetate, acetic acid-calcium acetate, acetic acid-magnesium acetate, and similar compounds. The preferred acetate buffer is acetic acid and sodium acetate. Pharmaceutical composition refers to a mixture comprising one or more of the compounds described herein, or physiologically / pharmaceutically acceptable salts or prodrugs thereof, and other chemical components, such as physiologically / pharmaceutically acceptable carriers and excipients. The purpose of the pharmaceutical composition is to maintain the stability of the active ingredient, promote delivery to the body, and facilitate absorption of the active ingredient to exert its biological activity. The pharmaceutical composition and the preparation used herein are not mutually exclusive. Unless otherwise specified, when referring to the solution form of the pharmaceutical composition described herein, the solvent is water. Lyophilized preparation refers to a pharmaceutical preparation or composition obtained after a lyophilization step (e.g., a vacuum lyophilization step) of the pharmaceutical composition in its liquid or solution form, or lyophilization of the preparation in its liquid or solution form. The term "approximately," as used herein, means that the value is within an acceptable error range of the specific value determined by experts in the field, q Lncnn / Lznz / E / Yii, and the value depends in part on how it is measured or determined (i.e., the limit of the measuring system). For example, "approximately" in this context refers to a standard deviation less than one or more than one. Alternatively, "approximately" refers to a range of up to 20%. Furthermore, particularly for biological systems or processes, the term means an order of magnitude of up to one, or up to 5 times greater than the value.Unless otherwise specified, the meaning of approximately XX or approximately XX or comprising substantially XX as used herein refers to a value within an acceptable error range of the specified value XX (which includes the value XX itself, as well as values ​​within an acceptable error range of the value as determined by experts in the field). The pharmaceutical composition described herein is capable of achieving a stable effect: the TGF-β receptor fusion protein or the pharmaceutical composition thereof substantially retains physical and / or chemical stability and / or biological activity after storage; preferably, the pharmaceutical composition substantially retains physical and chemical stability and biological activity after storage. Shelf life is generally determined based on the predetermined shelf life of the pharmaceutical composition. Many analytical techniques are currently available for measuring the stability of active ingredients, which can assess stability after storage at a given temperature for a specified period. A stable pharmaceutical preparation of antibody or protein is one for which no significant changes are observed under the following conditions: storage at a refrigerated temperature (2-8 °C) for at least 3 months, preferably for 6 months, more preferably for 1 year, and even more preferably for up to 2 years. In addition, stable liquid preparations include liquid preparations that exhibit desired characteristics after storage at a temperature (including 25 °C) for 1 month, 3 months, or 6 months, or storage at 40 °C for a period of 28 days. Typical acceptable standards for stability are as follows: as measured by SECHPLC, generally no more than approximately 10%, preferably no more than approximately 5%, of the active ingredients (such as proteins, antibodies) are degraded. By visual inspection, the pharmaceutical preparation is a pale yellow to nearly colorless, clear or colorless liquid, or clear white to slightly milky, or clear pale yellow to nearly colorless liquid. The change in concentration, pH, and osmolality of the preparation is no more than ±10%. Truncation is generally observed to be no more than approximately 10%, preferably no more than approximately 5%. Generally, no more than approximately 10%, preferably no more than approximately 5%, of the aggregates are formed. The active ingredient in the pharmaceutical preparation is considered to retain its physical stability if the antibody does not show any significant increase in aggregation, precipitation, and / or QLncnn / Lznz / B / Yi denaturation by visual inspection of color and / or clarity, or UV light scattering, size exclusion chromatography (SEG), and dynamic light scattering (DLS). Changes in protein conformation can be assessed by fluorescence spectroscopy (which determines the protein's tertiary structure) and by FTIR spectroscopy (which determines the protein's secondary structure). The active ingredient (such as a protein or antibody) in a pharmaceutical preparation is considered to retain its chemical stability if it does not exhibit any significant chemical changes. Chemical stability can be assessed by detecting and quantifying chemically altered forms of proteins or antibodies. Degradation processes that often lead to changes in the chemical structure of proteins include hydrolysis or truncation (assessed using methods such as size exclusion chromatography and SDS-PAGE), oxidation (assessed using methods such as peptide mapping combined with mass spectrometry or MALDI / TOF / MS, etc.), and deamidation (assessed using methods such as ion-exchange chromatography, capillary isoelectric focusing, peptide mapping, and measurement of isoaspartic acid content, etc.).) and isomerization (evaluated by measuring isoaspartic acid content, peptide mapping, etc.). An active ingredient (e.g., a protein or antibody) retains its biological stability in the pharmaceutical preparation if, for a given period of time, it exhibits biological activity within a predetermined range from the time the pharmaceutical formulation is prepared. The biological activity of an active ingredient (such as a protein or antibody) can be determined, for example, by antigen-binding assay. As used in the description, the three-letter code and the one-letter code for amino acids are as described in J. Biol. Chem, 243, p. 3558 (1968). As used in the present description, antibody refers to immunoglobulin, a four-peptide chain structure made up of two identical heavy chains and two identical light chains connected by disulfide bonds between chains. In the present description, the antibody light chain described herein further comprises light chain constant regions, comprising a human or murine κ, λ, λ chain, or a variant or variants thereof. In the present description, the antibody heavy chain described herein further comprises heavy chain constant regions comprising IgG1, IgG2, IgG3, IgG4 or variants thereof. At the N-terminal end of the antibody's heavy and light chains, a region of approximately 110 amino acids varies considerably, known as the variable region (Fv region); the amino acid sequence at the C-terminal end is relatively stable, known as QLncnn / Lznz / E / Yi constant region. The variable region comprises three hypervariable regions (HVRs) and four FR regions (FRs) with a relatively conserved sequence. Three hypervariable regions determine the specificity of an antibody, also known as the complementarity-determining region (CDR). Each light-chain variable region (LCVR or VL) and each heavy-chain variable region (HCVR or VH) is composed of three CDRs and four FRs, arranged from the amino terminus to the carboxyl terminus as follows: FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. The three light-chain CDRs are LCDR1, LCDR2, and LCDR3; the three heavy-chain CDRs are HCDR1, HCDR2, and HCDR3.The number and location of amino acid residues of the CDR region in the LCVR and HCVR regions of the antibody or antigen-binding fragment herein meet the known Kabat numbering criteria (LCDR1-3, HCDR1-3), or meet the Kabat and Chotia numbering criteria; Kabat numbering criteria (see Kabat et al (1991), Sequences of Proteins of Immunological Interest, 5th edition, Public Health Service, National Institutes of Health, Bethesda, MD), and Chotia numbering criteria (see Al-Lazikani et al (1997) JMB 273: 927-948). The antibody described herein comprises murine antibodies, chimeric antibodies, and humanized antibodies, preferably humanized antibodies. As used in this description, the “antibody” or “antibody-binding fragment” or “functional fragment” refers to the Fab fragment, Fab' fragment, or F(ab') 2 fragment that has antigen-binding activity, as well as the Fv fragment or scFv fragment that binds to the antigen. The Fv fragment is the minimal antibody fragment comprising all antigen-binding sites. The Fv fragment comprises a heavy-chain variable region and a light-chain variable region, but no constant regions. Generally, the Fv antibody further comprises a polypeptide linker between the VH and VL domains to form a structure necessary for antigen binding. In addition, different linkers can be used to connect the variable regions of two antibodies to form a polypeptide chain, called a single-chain antibody or single-chain Fv (sFv).As used herein, the term PD-L1 binding means the ability to interact with human PD-L1. As used herein, the term “antigen-binding site” refers to non-consecutive or consecutive three-dimensional sites on an antibody or antigen-binding fragment thereof that recognize and specifically bind to a target antigen. The term murine antibody, in this description, refers to the anti-human PD-L1 monoclonal antibody prepared according to current knowledge and skills. During preparation, the test subject is injected with PD-L1 antigen, and then the hybridoma-expressing antibody possessing the desired sequence or functional characteristics is isolated. The term “chimeric antibody” refers to an antibody formed by fusing the variable region of a non-human antibody (such as murine) with the constant region of a human antibody, to QLncnn / Lznz / E / Yi alleviates the immune response induced by non-human antibodies (such as murine). To establish a chimeric antibody, a hybridoma secreting a specific monoclonal antibody is first established, variable region genes are then cloned from hybridoma cells, and then human antibody constant region genes are cloned as desired. The non-human antibody variable region genes (such as murine) are ligated with human constant region genes to form a chimeric gene that can be inserted into a human vector, and the chimeric antibody molecule is finally expressed in an industrial eukaryotic or prokaryotic system. In a preferred embodiment of the present description, the chimeric antibody PD-L1 light chain further comprises light chain constant regions derived from the human k, oooo variant or variants thereof.The chimeric antibody PD-L1 heavy chain further comprises heavy chain constant regions derived from human IgG1, IgG2, IgG3, IgG4, or variant(s) thereof. The human antibody constant region(s) may be selected from heavy chain constant regions derived from human IgG1, IgG2, IgG3, IgG4, or variant(s) thereof, preferably comprising a heavy chain constant region derived from human IgG2 or IgG4, or IgG4 without ADCC (antibody-dependent cell-mediated cytotoxicity) due to amino acid mutation. The term humanized antibody, also known as a CDR-grafted antibody, refers to an antibody generated from non-human CDR sequences (such as murine) grafted onto the human antibody variable region framework. In other words, it is an antibody generated from different types of human germline antibody framework sequences. The humanized antibody overcomes the strong anti-antibody response induced by chimeric antibodies that carry a large number of non-human components (such as murine). Such framework sequences can be obtained from a public DNA database or published references covering germline antibody gene sequences. For example, human heavy and light chain variable region DNA sequences can be found in the VBase human germline sequence database (available at www.mrccpe.com.ac).uk / vbase), as well as those found in Kabat, EA et al. 1991, Sequences of Proteins of Immunological Interest, 5th Ed. To avoid the decrease in activity caused by reduced immunogenicity, the variable region framework of the human antibody undergoes minimal back mutation to maintain activity. The humanized antibody of the present description also refers to a humanized antibody that is further obtained by visualizing phages for the purpose of CDR affinity maturation. As used in this description, the term ADCC, that is, antibody-dependent cell-mediated cytotoxicity, refers to cells expressing Fe receptors that directly destroy antibody-coated target cells by recognizing the Fe segment of the antibody. The ADCC effector function of the antibody can be reduced or eliminated by modification of the Fe segment of IgG. This modification refers to mutations in the antibody's heavy chain constant region, such as mutations selected from the group consisting of N297A, L234A, and L235A mutations in IgG1; IgG2 / 4 chimera; or F234A / L235A mutations in IgG4. As used herein, identity indicates the degree of similarity between the sequences of two polynucleotides or two polypeptides. Sequence identity in this description is at least 85%, 90%, or 95%, preferably at least 95%. Non-exhaustive examples include, but are not limited to, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%. Comparison and determination of the percentage of identity between two sequences can be accomplished using the default settings of the BLASTN / BLASTP algorithm available on the National Center for Biotechnology Institute website. The term TGF-β receptor II or TORβKII or transforming growth factor receptor II refers to binding ligands (including, among others, TUΕβI, TUΡβ2 and TUΡβ3), through which cell surface receptors activate the intracellular signaling transduction pathway. The term PD-L1 refers to programmed cell death ligand 1, also known as CD274 and B7H1. PD-L1 is a 290-amino-acid protein with an extracellular IgV-like domain and an IgC-like domain (amino acids 19–239 of full-length PD-L1), a transmembrane domain, and an intracellular domain of approximately 30 amino acids. PD-L1 is constitutively expressed in many cells, including antigen-presenting cells (such as dendritic cells, macrophages, and B lymphocytes), as well as hematopoietic and non-hematopoietic cells (such as vascular endothelial cells, pancreatic islets, and immunologically privileged sites). PD-L1 is also expressed in a variety of tumor and virus-infected cells and is a member of the immunosuppressive environment (Ribas 2012, NEJM 366: 2517–2519). PD-L1 binds to one of two T lymphocyte co-inhibitors (PD-1 and B7-1). The PD-L1 antibody or antigen-binding protein described herein includes any anti-PD-L1 antibody or antigen-binding fragment described herein. The anti-PD-L1 antibody may be a commercially available PD-L1 antibody or one disclosed in publications, including, but not limited to, BMS-936559, MPDL3280A, MEDI4736, MSB0010718C (see US2014341917, US20130034559, US8779108), and similar publications. The antibody may be a monoclonal antibody, a chimeric antibody, a humanized antibody, or a human antibody. The antibody fragment includes a Fab fragment, Fab' fragment, F(abj 2) fragment having antigen-binding activity, and Fv fragment and scFv fragment binding to the antigen. As an example of a preparation process for the PD-L1 antibody of the present description, published in PCT application PCT / CN2016 / 104320 (PCT Publication No. WO2017084495), the PD-L1 antibody comprises CDRen sequences of heavy chain variable regions as described QLncnn / Lznz / E / Yi next: HCDR1: SYWMH SEQ ID NO: 1 HCDR2: RI XiPNSG X2TSYNEKFKN SEQ ID NO:2 HCDR3: GGSSYDYFDY SEQ ID NO:3. In an alternative mode, Xi is selected from H or G; and X2 is selected from G or F. In another embodiment, an exemplary PD-L1 antibody of the present description further comprises CDR sequences of a light chain variable region as described below: LCDR1: RASESVSIHGTHLMH SEQ ID NO:4 LCDR2: AASNLES SEQ ID NO:5 LCDR3: QQSFEDPLT SEQ ID NO:6. In another modality, the previous CDR regions are humanized using a CDR grafting strategy, and the FR of the humanized light chain templates are IGKV7-3*01 and hjk2.1, the FR of the humanized heavy chain templates are IGHV1-46*O1 and hjh6.1, and the humanized variable region sequences are as follows: The variable region of the humanized PD-L1 antibody heavy chain: OVOLVQSGAEVKKPGASVKVSCKASGYTFTSXWMYIWVROAPGOGLEWMG^XyVNS^^ ΎlAEEYP3ARVTMTRDTSTSΊVYMELSSLRSEDTAl·ΎYCARGG?,S^ΎΌΎΈΌΎWG0GΊTVTVSS. SEQ ID NO:7, where Xi is selected from H or G; and X2 is selected from G or F. The variable region of the humanized PD-L1 antibody light chain: DTELWPAXMESPGQRmrCRASESVSIHGTHLMHIFEOGXPGOPPXLLZrAASNLESGEPA RFSGSGSGTDFTLTINPVEANDTANYYCQQSYEOPLYFGQGTKLEIK SEQ ID NO:8; NOTE: The order is FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4, the italicized part represents the FR sequence and the underlined part represents the CDR sequence (the amino acid residues of CDR are determined and indicated according to Kabat numbering criteria). In another modality, the design for back mutations in the humanized antibody of the present description is carried out, and the designed back mutations are shown in Table 1 below: Table 1. Back-mutation design QLncnn / Lznz / E / Yi VL VH VL.l grafted VH. 1 grafted VL. 1A Y91F VH. 1A T74K VL.1B Y91F, G72E VH. IB T74K, R72V, M48I, M70L VL.1C Y91F, G72E, T22S VH.1C T74K, R72V, M48I, M70L, R38Q VH.1D T74K, R72V, M48I, M70L, R38Q, L83F VH.1E T74K, R72V, M48I, M70L, R38Q, L83F, V68A, V79A q Lncnn / Lznz / E / Yii Note: For example, Y91F indicates a Y-to-F back mutation at position 91 according to natural numbering. “Grafted” indicates that the murine antibody CDR is implanted into human germline FR sequences. New humanized antibodies can be obtained through various combinations of heavy chain and light chain mutations shown in Table 1. In another aspect of the description, a method for constructing a humanized clone is provided, as follows: Primers and VH / VK gene fragments were designed from each PCR-humanized antibody and then inserted into a pHr expression vector fragment (which has a signaling peptide and constant region gene (CH1-Fc / CL)) to carry out homologous recombination, in order to design a full-chain antibody expression vector: VH-CH1-Fc-pHr / VK-CL-pHr. 1. Primer design: The online software DNAWorks (v3.2.2) (http: / / helixweb.nih.gov / dnaworks / ) was used to design multiple primers for VH / VK synthesis comprising gene fragments required for recombination: 5'-30bp signaling peptide + VH / VK + 30bp CH1 / CL-3'. 2. Cutting and splicing fragments: According to the TaKaRa DNA polymerase STAR GXL Primer manuals, using the primers designed above, VH / VK comprising gene fragments necessary for recombination was obtained by two-step PCR amplification. 3. Design and enzymatic digestion of the pHr expression vector (which has a signaling peptide and a constant region gene fragment (CH1-FC / CL)): The pHr expression vector (containing a signaling peptide and a constant region gene fragment (CH1-FC / CL)))) was designed and structured using a special restriction endonuclease, such as BsmBI, which recognizes the distinctive feature between the sequence and the restriction site. The vector was digested using BsmBI, and the digested fragments were then extracted using a gel and stored for later use. 4. Recombinant design of the VH-CH 1-Fc-pHr / VK-CL-pHr expression vector VH / VKs comprising gene fragments required for recombination and the pHr expression vector (which had a signaling peptide fragment and a constant region gene (CH1)) were added Fc / CL)) that has been digested with BsmBI in DH5H-competent cells in a 3:1 ratio, were incubated at 0 °C on ice for 30 min, thermally shaken at 42 °C for 90 s, 5 volumes of LB medium were added and then incubated at 37 °C for 45 min, then plated onto LBAmp plates, and cultured at 37 °C overnight. A single clone was selected for sequencing and a clone of interest was obtained. 5. The plasmid was designed according to the design in the present example, then the purified protein was expressed and the affinity of the resulting protein was quantified by the detection described in the SPR Example. 6. Finally, the affinity of the humanized backmutation mutant or hybridoma antibodies with human PD-Ll-his was quantified using BIACORE; the humanized backmutation sites and the sequence combinations obtained from the selection are as follows: The PD-L1 antibody heavy chain variable region: OVOLVOSGAEVKKPGASVKVSCKASGYTFTS'T^MHWVROAPGQGLEWMG^G^SGFfSY lAYKFYGARVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGG'&SYOYYOYWGOGTTVTVSS SEQ ID NO:9; where HCDR2 is as shown in RIGPNSGFTSYNEKFKN SEQ ID NO: 10, i.e., Xi in SEQ ID NO: 7 is G, and X2 in SEQ ID NO: 7 is F; The PD-L1 antibody light chain variable region: D7E¿TQS.m¿.4ES.PGO&4nTCRASESVSIHGIHLMH)TOOÁ?GQP^^ RFSGSGSGTDFTLTINPVEAEDTANYYCQQSFEOYEÍFGQGTKLEIK SEQ ID NO: 11; NOTE: The order is FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4, the italicized part represents the FR sequence and the underlined part represents the CDR sequence (the amino acid residues of CDR are determined and indicated according to Kabat numbering criteria). In another aspect of this description, a method for constructing and expressing a human IgG4-type anti-PD-L1 antibody is provided, and a PD-L1 antibody used for designing fusion proteins is also provided. The PD-L1 antibody can also be used as a control molecule in the Test Examples of this description. Since PD-L1 is also expressed on activated T lymphocytes, the use of wild-type IgG1 constant regions can cause Fe-mediated effects (such as ADCC and CDC), which could result in a reduction of activated T lymphocytes. The present description selected mutated IgG4 to obtain antibodies without ADCC and CDC. The clone obtained by affinity maturation was converted to IgG4-like, and the central hinge region of IgG4 comprises the S228P mutation (corresponding to position 227 in the natural sequence of SEQ ID NO: 12), the F234A mutation (corresponding to position 233 in the natural sequence of SEQ ID NO: 12), and the L235A mutation (corresponding to position 234 in the natural sequence of QLncnn / Lznz / E / Yi SEQ ID NO: 12) were additionally introduced (mAbs 4:3, 310-318; May / June 2012). Simultaneously, to avoid the breakage that occurred at the C-terminus of the antibody heavy chain when the linker peptide (used to link the extracellular domain TGF-pRII) was introduced, K at the terminal position of the PD-L1 antibody heavy chain was further mutated to A (corresponding to the last position in the natural sequence of SEQ ID NO: 12), in order to increase the stability of the fusion protein. The PD-L1 antibody sequence of the present description used for the construction of fusion proteins is as follows: PD-L1 antibody heavy chain: IgG4 (AA) (S228P) QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGRIGPNSGF TSYNEKFKNRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGSSYDYFDYWGQGTTVTVSSAS TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVV TVPSSSLGTKIYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAdGGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKE YKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGA SEQ ID NO: 12; OBSERVATION: The underlined part is the heavy chain variable region sequence and the ununderlined part is the heavy chain constant region sequence (the italicized part is the mutation site); PD-L1 light chain antibody: DIVLTOSPASLAVSPGORATITCRASESVSIHGTHLMHWYOOKPGOPPKLLIYAASNLESGV PARFSGSGSGTDFTLTINPVEAEDTANYYCOOSFEDPLTFGOGTKLEIKRTVAAPSVFIFPPSDEQLK SGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHK VYACEVTHQGLSSPVTKSFNRGEC SEQ ID NO: 13; NOTE: The underlined part is the light chain variable region sequence and the ununderlined part is the light chain constant region sequence. As used herein, a fusion protein described herein is a protein product obtained by the co-expression of two genes using recombinant DNA technology. Methods for producing and purifying antibodies and antigen-binding fragments are known in the field and can be found (e.g., in Antibodies, A Laboratory Manual, Coid, Spring Harbor, chapters 5-8 and 15). For example, mice can be immunized with human PD-L1 or fragments thereof, and the resulting antibodies can be re-naturalized, purified, and sequenced for amino acid sequences using conventional methods known in the field. QLncnn / Lznz / E / Yi matter. Antigen-binding fragments can also be prepared using conventional methods. The antibody or antigen-binding fragments described herein are genetically modified to graft non-human antibody-derived CDRs onto one or more human FRs. By aligning against the IMGT human antibody variable region germline database using MOE software, the human frame germline sequences can be obtained from the ImMunoGeneTics (IMGT) website http: / / imgt.cines.fr, or from The Immunoglobulin Facts Book, 2001, ISBN 012441351. The genetically modified antibodies or antigen-binding fragments described herein can be prepared and purified using known methods. For example, cDNA sequences encoding a heavy and a light chain can be cloned and genetically modified into a GS expression vector. The genetically modified immunoglobulin expression vector can be stably transfected into CHO cells. As a more widely recommended method, the mammalian expression system will result in glycosylation of the antibody, typically at highly conserved N-terminus sites in the Fe region. Stable clones can be obtained by expressing an antibody that binds specifically to human PD-L1. Positive clones can be expanded in serum-free culture medium for antibody production in bioreactors.The culture medium, into which the antibody has been secreted, can be purified using conventional techniques. For example, the medium can be loaded onto a Sepharose FF protein A or G column equilibrated with a compatible buffer. The column is washed to remove nonspecific binding components. The bound antibody is eluted using a pH gradient, and the antibody fractions are detected by SDS-PAGE and then collected. The antibody can be filtered and concentrated using common techniques. Soluble aggregates and multimers can be effectively removed using common techniques, including size exclusion or ion exchange. The product can be frozen immediately, for example, at -70 °C, or it can be lyophilized. The immunoregulatory molecule described herein can be used to attenuate the immune tolerance of cancer cells. This description utilizes a truncated form of the extracellular domain of TGF-βRII as the immunoregulatory molecule in the fusion protein. The TGF-β II receptor (TGF-βRH) binds to the ligands TGF-βI and TOR-β3 with high affinity. The TGF-β RII / TGF-β complex recruits TGF-β RI to form a signal transduction complex (Won et al., Cancer Res. 1999; 59: 1273-7). The extracellular TGF-BRII domain is a peptide of amino acid residue 136 from the N-terminus of extracellular TGF-BRII, an example of which is shown in SEQ ID NO: 14. Other variants of approximately 136 amino acids in length and derived from the human extracellular TGF-BRII domain, which can bind to TGF-β1 and TOR-β3, also belong to the extracellular TGF-BRII domain described herein. The present description has found the structure and function of the truncated form The consecutive N-terminus of the TGF-βRII extracellular domain is more stable than that of the untruncated molecule. A fusion protein comprising the unmanned N-terminus form of the TGF-βRII extracellular domain (a polypeptide shown as aa.1-136 of SEQ ID NO:14) is susceptible to cleavage. In particular, the TGF-βRII extracellular domain truncated by fewer than 26 consecutive amino acids from the N-terminus is more stable; preferably, the TGF-βRII extracellular domain truncated by 14-26, and more preferably, truncated by 14-21 consecutive amino acids from the N-terminus, has a higher expression level; and more preferably, truncated by 19 or 21 consecutive amino acids. The term TGF-β receptor fusion protein refers to a fusion protein comprising the TGF-β receptor. In some embodiments, the TGF-β receptor fusion protein described herein is the TGF-β receptor fusion protein described in International Patent Application PCT / CN2018 / 086451 (WO 2018205985A1). The entire content of WO 2018205985A1 is incorporated herein in its entirety.In some embodiments, the TGFβ receptor fusion protein is a PD-L1 antibody / TOR-βKII extracellular domain fusion protein (PD-L1 / TGF-β trap), with the TGF-ββII extracellular domain serving as the immunoregulatory molecule portion of the fusion protein, the PD-L1 antibody serving as the target-specific portion of the fusion protein, the TGF-βKII extracellular domain (e.g., shown as SEQ ID NO: 14, 15, 16, or 17) connecting to the C-terminal end (also known as the carboxy terminus) of the PD-L1 antibody heavy chain via a linker sequence (e.g., (G4S)xG, where x is 3-6) to form a fusion sequence, and the fusion sequence connecting to the PD-L1 antibody light chain via interchain disulfide bonds to ultimately form the fusion protein PD-Ll / TGF-β trap, the structure is shown in Figure 1.In some modalities, the TGF-β receptor fusion protein is the fusion protein described in Table 2 of Example 1 of the description. The term linker or linking sequence refers to a connecting peptide sequence used to link protein domains, generally with a degree of flexibility, and the use of linkers will not lead to the loss of the original function of the protein domain. In some embodiments of the present description, the linking sequence is (G4S)XG, where x is 3-6; for example, the linking sequence is a polypeptide such as: (G4S)3G, (G4S)4G, (G4S)sG, or (G4S)eG. Conservative modification, replacement, or substitution refers to substituting amino acids in a protein with other amino acids that have similar characteristics (e.g., charge, side chain size, hydrophobicity / hydrophilicity, conformation, and rigidity of the main structure, etc.), so that changes can be made frequently without altering the protein's biological activity. Experts in the field recognize that, generally speaking, substituting single amino acids in the non-essential region of a polypeptide does not substantially alter biological activity (see, for example, Watson et al. (1987) Molecular Biology of the Gene, The q Lncnn / Lznz / E / Yii Benjamin / Cummings Pub. Co., p224 (4th edition). In addition, substitutions of structurally or functionally similar amino acids are less likely to disrupt biological activity. “Optional” or “optionally” means that the following event or situation may occur, but is not necessarily so, and the description includes cases where the event or circumstance does or does not occur. For example, “optionally comprising 1-3 antibody heavy chain variable regions” means that the antibody heavy chain variable region with a specific sequence may be present, but is not necessarily so. The terms "administered," "administered," and "treatment," as applied to an animal, human, experimental subject, cell, tissue, organ, or biological fluid, refer to the contact of a pharmaceutical, therapeutic, diagnostic, or exogenous composition agent with the animal, human, subject, cell, tissue, organ, or biological fluid. "Administered," "administered," and "treated" may refer, for example, to therapeutic, pharmacokinetic, diagnostic, research, and experimental methods. The treatment of a cell comprises contacting a reagent with a cell, as well as contacting a reagent with a fluid, where the fluid is in contact with the cell. "Administration," "administered," and "treatment" also mean in vitro and ex vivo treatments of, for example, a cell by means of a reagent, a diagnostic composition, a binding composition, or another cell.Administration or treatment, as applied to a human, veterinary, or research subject, refers to therapeutic treatment, prophylactic or preventive measures, research and diagnostic applications. Treatment means administering a therapeutic agent, such as a composition described herein, internally or externally, to a subject who has one or more symptoms of a disease for which the agent has known therapeutic activity. The agent is usually administered in an amount effective in relieving one or more symptoms of the disease in the subject or population being treated, inducing regression, or preventing the progression of such symptoms to a clinically quantifiable degree. The amount of a therapeutic agent that is effective in relieving any particular symptom of the disease (also called the therapeutically effective amount) may vary according to factors such as the stage of the disease, the age and weight of the subject, and the agent's ability to elicit a desired response in the subject.Whether a disease symptom has been relieved can be assessed by any clinical measurement generally used by physicians or other qualified healthcare providers to evaluate the severity or progression of the symptom. While a modality described herein (e.g., a treatment method or manufactured item) may not be effective in relieving the symptoms of the target disease in every subject, it should relieve the symptoms of the target disease in a statistically significant number of subjects as determined by any known statistical test in the art, such as the Student's t-test, the chi-square test, or the Mann-Whitney U test. Whitney, the Kruskal-Wallis test (H test), the Jonckheere-Terpstrast test, and the Wilcoxon test. An effective amount is a quantity sufficient to improve or prevent a symptom or sign of a disease. It also means a quantity sufficient to permit or facilitate diagnosis. An effective amount for a particular animal or veterinary subject may vary depending on factors such as the condition being treated, the subject's overall health, the route and dosage of administration, and the severity of side effects. An effective amount may be the maximum dosage or dosage protocol that avoids significant side effects or toxicity. The Tm value refers to the temperature at which thermal denaturation of a protein occurs; that is, the temperature at which half of the protein unfolds. At this point, the protein's spatial structure is destroyed. Therefore, the higher the Tm value, the greater the thermal stability of the protein. Substitution refers to replacing the solvent system that dissolves the antibody protein. For example, the high-salt or hypertonic solvent system containing the antibody protein is replaced using physical methods against a buffer system to create a stable preparation, so that the antibody protein is present in the stable preparation. Physical methods include, but are not limited to, ultrafiltration, dialysis, or reconstitution after centrifugation. Detailed description of the invention Hereafter, this description is further elaborated upon with reference to examples, test examples, or preparation examples. However, these examples, test examples, or preparation examples are for illustrative purposes only, and the scope of this description is not limited to them. In the examples, test examples, or preparation examples in this description, when no specific conditions are described, they are generally carried out under conventional conditions or conditions proposed by the manufacturers of the materials or products. When the source of the reagents is not specifically indicated, the reagents are conventional reagents that are commercially available. EXAMPLES Example 1: Cloning and expression of PD-LÍ / TGF-β trap fusion protein The extracellular domain of TOE-βKIII (full chain or truncated form of SEQ ID NO: 14) was used as the part for the immunoregulatory molecule in the fusion protein, and the PD-L1 antibody is used as a selectively acting part of the fusion protein to form a PD-Ll antibody / TGF-βHII extracellular domain fusion protein (PD-Ll / TGF-β trap). QLncnn / Lznz / E / Yi Unexpectedly, it was discovered that the truncated form of the extracellular domain TGF-βRP is relatively stable, especially more stable after being truncated by less than 26 amino acids from its N-terminal end, preferably, a higher expression level and a more stable structure are obtained after being truncated by 14-26 amino acids, more preferably by being truncated by 14-21 consecutive amino acids from the N-terminal end, and most preferably by being truncated by 14, 19 or 21 consecutive amino acids from the N-terminal end. The sequences of the non-limiting examples of the extracellular domain TGF^RII and its truncated form in the present description are as follows: TGF^RII extracellular domain sequence: ECD (1-136) IPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSITSICEKPQEVC VAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFS EEYNTSNPD SEQ ID NO: 14; Extracellular RII domain sequence of TGF-β, with a truncation or deletion of 19 amino acids at the N-terminal end: ECD (20-136) GAVKFPQLCKFCDVRFSTCDNQKSCMSNCSITCICEKPQEVCVAVWRKNDENITLETVCH DPKLPYHDFILEDAASPKCIMKKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD SEQ ID NO: 15; RII extracellular domain sequence of TGF-β, with a truncation or deletion of 21 amino acids at the N-terminal end: ECD (22-136) VKFPQLCKFCDVRFSTCDNQKSCMSNCSITCICECPQEVCVAVWRKNDENITLETVCHDPK LPYHDFILEDAASPKCIMKKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD SEQ ID NO: 16; Extracellular RII domain sequence of TGF-β, with a truncation or deletion of 14 amino acids at the N-terminal end: ECD (15-136) VTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSITCICEKPQEVCVAVWRKNDENITL ETVCHDPKLPYHDFILEDAASPKCIMKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPD SEQ ID NO: 17. As an example, the C-terminal heavy chain amino acid of the PD-L1 antibody of the present description (a PD-L1 antibody, wherein the heavy chain is shown as SEQ ID NO: 12, and the light chain is shown as SEQ ID NO: 13) was ligated to the extracellular domain TGF^RII with variable lengths by means of a linker (G+SjxG (x is 3-6), by homologous recombination technique, and was conventionally expressed in an expression system 293 together with the PD-L1 antibody light chain, and the fusion proteins obtained are shown in Table 2: QLncnn / Lznz / E / Yi Table 2. PD-Ll antibody / extracellular domain TGF-βHII fusion protein Fusion Protein Sequence Description Number of Consecutive Amino Acids Removed at N-End Fusion Protein 1 Ab-(G4S)4G-ECD (1-136) No Removal Fusion Protein 2 Ab-(G4S)3G-ECD (15-136) 14 Fusion Protein 3 Ab-(G4S)3G-ECD (15-136, N19A) 14 Fusion Protein 4 Ab-(G4S)3G-ECD (20-136) 19 Fusion Protein 5 Ab-(G4S)3G-ECD (22-136) 21 Fusion Protein 6 Ab-(G4S)3G-ECD (27-136) 26 Fusion Protein 7 Ab-(G4S)4G-ECD (15-136) 14 Fusion Protein 8 Ab-(G4S)4G-ECD (15-136, N19A) 14 Fusion protein 9 Ab-(G4S)4G-ECD (20-136) 19 Fusion protein 10 Ab-(G4S)4G-ECD (22-136) 21 Fusion protein 11 Ab-(G4S)4G-ECD (27-136) 26 Fusion protein 12 Ab-(G4S)5G-ECD (15-136) 14 Fusion protein 13 Ab-(G4S)5G-ECD (15-136, N19A) 14 Fusion protein 14 Ab-(G4S)5G-ECD (20-136) 19 Fusion protein 15 Ab-(G4S)5G-ECD (22-136) 21 Fusion protein 16 Ab-(G4S)5G-ECD (27-136) 26 Fusion protein 17 Ab-(G4S)6G-ECD (27-136) 26 q Lncnn / Lznz / E / Yi Note: Ab represents the PD-L1 antibody of the present description (the heavy chain shown as SEQ ID NO: 12, and the light chain shown as SEQ ID NO: 13); ECD (n-136) in the sequence description represents the truncated or full-chain form of the TGFβMI extracellular domain; n represents the initial amount of amino acid after truncation of the TGFβKIII extracellular domain. The structure of the fusion protein of the present description is shown in Figure 1; N19A indicates that the amino acid at position 19 of the full-length TGF-βKIII extracellular domain (SEQ ID NO: 14) is mutated from N to A. The nucleotide sequence encoding the PD-L1 antibody, the nucleotide sequence encoding the extracellular domain TGF-βHII, and the nucleotide sequence of the linking protein fragment ((GS)XG) were obtained using conventional techniques. The C-terminal nucleotide of the PD-L1 antibody was ligated via the linking protein to the N-terminal nucleotide of the extracellular domain TGF-βHII of varying lengths using homologous recombination techniques, and then cloned into the Phr-Bsmbl vector. A recombinant PD-L1 / TGF-β trap was expressed in 293 cells and purified as described in Example 2. The purified protein can be used in the experiments of the following examples. Example 2: Purification of PD-Ll / TGF-β trap fusion protein The cell culture medium was centrifuged at high speed, the supernatant was collected, and the first purification step was performed using affinity chromatography. The chromatographic medium was Protein A or an Fe-interacting packing agent, such as Mabselect GE. The equilibration buffer was UPBS (137 mmol / L NaCl, 2.7 mmol / L KCl, 10 mmol / L Na₂HPO₄, 2 mmol / L KH₂PO₄, pH 7.4). After equilibrating 5 x column volumes, the cell supernatant was loaded for binding, and the flow rate was controlled to allow the sample to remain on the column for > 1 min. After loading the sample, the column was washed with UPBS (pH 7.4) until the UV A280 absorbance was reduced to the baseline value. Next, the column was washed with 0.1 M glycine elution buffer (pH 3.0), and the eluted peak was collected according to the UV A280 absorption peak, and the collected eluted sample was neutralized with 1 M Tris (pH 8.5). The neutralized eluted sample was concentrated by ultrafiltration and then subjected to size exclusion chromatography. The buffer was 1*PBS and the column was an XK26 / 60 Superdex 200 (GE). The flow rate was controlled at 4 mL / min, the loading volume was less than 5 mL, and the target protein peak was clustered according to UV A280 absorbance. The purity of the collected protein was greater than 95%, as identified by SEC-HPLC and verified by LC-MS. The verified sample was aliquoted for use. The PD-L1 / TGF-β trap was obtained. The performance and beneficial effect of the PD-Ll / TGF-β trap fusion protein described herein are verified by biochemical testing methods as indicated below. Example of a test (Biological evaluation in vivo, in vitro) Example test 1 In vitro ELISA detection of PD-Ll / TGF-β trap binding to TGFβα The detection process is described as follows: a. The 96-well plates were coated with 100 pL / well of human TGF-βI (8915LC, CST) at a concentration of 1 pg / mL at 4 °C overnight. b. Wash 3 times with 250 pL of 1 xPBST, then add 250 pL of 5% milk PBS to block at 37 °C for 2 hours. c. Three washes were added with 250 pL of 1 xPBST, PD-L1 / TGFβ trap gradient dilutions, and TGF-β trap was used as a positive control and incubated for 1 hour at 37 °C. QLncnn / Lznz / B / Yi d. Wash 3 times with 250 pL 1 xPBST. e. 100 pL of anti-human Fc-HRP antibody (1:4000) was added to each well and incubated for 40 minutes at 37 °C. f. 100 pL of TMB were added to each well, incubated for 10 minutes at room temperature, and the reaction was stopped by adding 100 pL of 1 M H2SO4. g. Absorbance at 450 nm was quantified on a microplate reader and the data were analyzed using Graphpad Prism 5. The results of the in vitro binding of fusion proteins to human TGF-βI are shown in Figures 2 and 3. The ELISA showed that fusion protein 1 in Table 2 did not retain binding activity to human TGF-βI. Mass spectrometry analysis showed that fusion protein 1 (i.e., the untreated form of the extracellular domain TOE-βHII (1-136)) was unstable and easily cleaved into the heavy chain TOR-βMI, and the positive control had the same defect. Fusion proteins comprising the truncated form of the N-terminal end of the extracellular domain TORβRII, such as fusion proteins 7, 9, 10, and 12-15, specifically bind to human TGF-βI. Example test 2 In vitro ELISA detection of PD-Ll / TGF-β trap binding to PD-L1 Antigen used for detection: PD-Ll-His FTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQH SSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRIL VVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFY CTFRRLDPEENHTAELVIPELPLAHPPNEREQKLISEEDLHHHHHH SEQ ID NO: 18. The detection process is described as follows: a. The 96-well plates were coated with 100 pL / well of human PD-Ll-His (SEQ ID NO: 18) at a concentration of 5 pg / mL at 4 °C overnight. b. Wash 3 times with 250 pL of 1 xPBST, then add 250 pL of 5% milk PBS to block at 37 °C for 2 hours. c. Three washes were added with 250 pL of 1 xPBST, PD-L1 / TGFβ trap gradient dilutions and PD-L1 antibody as a positive control and incubated for 1 hour at 37 °C. d. Wash 3 times with 250 pL 1 xPBST. e. 100 pL of anti-human Fc-HRP antibody (1:4000) were added to each well and incubated for 40 minutes at 37 °C. f. 100 pL of TMB were added to each well, incubated for 10 minutes at room temperature, and the reaction was stopped by adding 100 pL of 1 M H2SO4. g. The absorbance at 450 nm was quantified using a microplate reader and the data were analyzed QLncnn / Lznz / B / Yi using Graphpad Prism 5. The results of in vitro binding of the fusion proteins described herein to human PD-L1 are shown in FIGURE 4. The ELISA showed that all fusion proteins retained binding activity to human PD-L1. Example test 3 Detection of PD-l / PD-L pathway blockade in vitro 1. Purpose of the test: In order to investigate the blocking effect of the PD-Ll / TGF-β trap on the PD-l / PD-LI signaling pathway, an antibody-blocking experiment was performed using cells carrying human PD-1 and PD-L1 receptor molecules that were designed by Promaga, respectively. 2. Problem samples Φ PD-L1 Antibody with heavy chain shown as SEQ ID NO: 12, and light chain shown as SEQ ID NO: 13; ® Control 1 (20T-Fc): ECD(20-136)-Fc, a fusion protein comprising a truncated TOE-βKII extracellular domain fragment ECD (20-136) and Fe, and the sequence is as follows: GAVKFPQLCKFCDVRFSTCDNQKSCMSNCSITCICECPQEVCVAVWRKNDENITLETVCH DPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEYNTSNPDAESKYGPPCP PCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSQEDPEVQFNWYVDGVEVHNAKTKPR EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSIEKTISKAKGQPREPQVYTLPPSQEE MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYCTTTPPVLDSDGFFFLYSRLTVDKSRWQEGNV FSCSVMHEALHNHYTQKSLSLSLG SEQ ID NO: 19; Control 2 (22T-Fc): ECD(22-136)-Fc, a ΤΟΡ-βΚΙΙ extracellular domain fragment fusion protein truncated ECD (22-136) and Fe, and the sequence is as follows: VKFPQLCKFCDVRFSTCDNQKSCMSNCSITCICECPQEVCVAVWRKNDENITLETVCHDPK LPYHDFILEDAASPKCIMKKKKPGETFFMCSCSDECNDNIIFSEEYNTSNPDAESKYGPPCPPCP APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVVHNACTKPREE QFNSTYRVVSVLTVLHQDWLNGI <EYI<CI<VSNI<GLPSSIEKTISI<AI<GQPREPQVYTLPPSQEEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFS CSVMHEALHNHYTQKSLSLSLG SEQ ID NO:20; Φ TGF-β receptor fusion protein prepared in Example 1 of the present disclosure: fusion protein 9, fusion protein 15: In fusion protein 9, the fusion peptide sequence of heavy chain ECD of PD-L1 antibody (G4S)4G-TGF^ RII (20-136) is as follows: QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGRIGPNSGF TSYNEKFKNRVTMTRDTSTSTVMELSSLRSEDTAVYCARGGSSYDYFDYWGQGTTVSSAS QLncnn / Lznz / B / Yi TKGPSVFPPLAPCSRSTSTEALGCLVKDYFPEPPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSSVV TVPSSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNACTKPREEQFNSTYRVVSVLTVLHQDWLNGKE YKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDfAVEWESN GQPENNYKTTPPVLDSDGFFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGAG' GG'GVGGGGAWGGSrfGG'G'.SrfGAVKFPOLCK^^ WRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEEY NTSNPD SEQIDNO:23; NOTE: The regular font is the PD-L1 antibody heavy chain sequence, the italics are the linker sequence, and the underline is the ECD (20-136) truncated fragment sequence of the TGF-pRII extracellular region. The light chain sequence of the PD-L1 antibody in fusion protein 9 is as follows: DIVLTQSPASLAVSPGQRATITCRASESVSIHGTHLMHWYQQKPGQPPKLLIYAASNLESGV PARFSGSGSGTDFTLTINPVEAEDTANYYCQQSFEDPLTFGQGTKLEIKRTVAAPSVFIFPPSDEQLK SGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHK VYACEVTHQGLSSPVTKSFNRGEC SEQ ID NO: 13; The ECD RII G-TGF-β fusion peptide sequence of the PD-L1 antibody chain pcsadafGíSf (22-136) in the f5 fusion protein is as follows: QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGRIGPNSGF TSYNEKFKNRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGSSYDYFDYWGQGTTVTVSSAS TKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVV TVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKE YKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGAG GGG5GGGG5GGGGSGGGGSGGGG5GVKFPQLCKFCDVRFSTCDNQKSCMSNCSITS1CEKPQEV CVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIF SEEYNTSNPD SEQ ID NO:24; NOTE: The regular font is the PD-L1 antibody heavy chain sequence, the italics are the linker sequence, and the underline is the sequence of the truncated ECD fragment (22-136) of the TGF-pRII extracellular region. The light chain sequence of the PD-L1 antibody in fusion protein 15 is as follows: QLncnn / Lznz / B / Yi DIVLTQSPASLAVSPGQRATITCRASESVSIHGTHLMHWYQQKPGQPPKLLIYAASNLESGV PARFSGSGSGTDFTLTINPVEAEDTANYYCQQSFEDPLTFGQGTKLEIKRTVAAPSVFIFPPSDEQLK SGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHK VYACEVTHQGLSSPVTKSFNRGEC SEQ ID NO: 13; © Human IgG: blank control, human immunoglobulin obtained from mixed normal human serum by purification using a conventional affinity chromatography method such as Protein A; i® Positive control (FP17022): PD-L1 antibody extracellular domain 2 / TGF-pRII fusion protein; The amino acid sequence of light chain 2 of antibody PD-L1 in fusion protein FP17022: QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSNRPSGVS NRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTRVFGTGTKVTVLGQPKANPTVTLFPPSSEE LQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASSYLSLTPEQWKSHR SYSCQVTHEGSTVEKTVAPTECS SEQIDNO:21; The fusion peptide amino acid sequence of PD-L1 antibody chain 2 heavy chain / TGFPRII extracellular domain (1-136) in FP17022 fusion protein: EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYIMMWVRQAPGKGLEWVSSIYPSGGITFY ADTVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYCARIKLGTVTTTVDYWGQGTLVTVSSASTK GPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPPVTSWNSGALTCGVHTFPAVLQSSGLYSLSSSVVT VPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS RTPEVTCVVVDVSHEDPEWKFNWYVDGVEVHNACTKPREEQYNSTYRVVSVLTVLHQDWLNG KEYCKKVSNCALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWE SNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG AGGGGSGGGGGGGGGGSGIPPHVQKSVNNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQ KSCMSNCSITSICEKPQEVCVAVWRKNDENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPG ETFFMCSCSSDECNDNIIFSEEYNTSNPD SEQ ID NO:22; 3. Test Process CHO / PD-L1 cells (CS187108, Promega) were digested and resuspended in complete F-12 nutrient mix medium (Ham). Cell density was adjusted to 4 × 10⁵ / mL using complete medium according to cell count results. The cell suspension was transferred to a loading tank, added to a 96-well plate at 100 pL / well using a multichannel pipette, and incubated at 37 °C in a 5% CO₂ incubator for 20–24 h. The Jurkat / PD-1 cell suspension (CS187102, Promega) was prepared the following day, and the cells were resuspended according to cell count results. QLncnn / Lznz / E / Yi using an assay medium, and the cell density was adjusted to 1.25 × 10⁶ / mL; cell culture plates comprising Cho / PD-L1 cells were removed from the incubator, 95 pL of the culture solution was withdrawn per well using a multichannel pipette, and gradient-diluted fusion protein, PD-L1 antibody, and positive control (FP17022) were added to 40 pL / well, respectively. The Jurkat / PD-1 cell suspension was then transferred to a loading tank, added to the cell culture plate at 40 pL / well, and incubated at 37 °C, 5% CO₂ for 5–6 h. During the protein incubation, the Bio-Glo™ reagent was removed and allowed to return to room temperature. The cell culture plates were removed and placed at room temperature for 5-10 minutes.Then 40 pL of dercactlvo Blo G1° ™ was added to each well, incubated in a safety cabinet for 5-10 min and the chemiluminescence signal value was read using a multifunction microplate reader. 4. Results As shown in Figure 5, similar to the positive control molecule, fusion protein 9 described herein was able to effectively block the binding of PD-1-expressing Jurkat cells to ChoO / PD-L1 cells, and the drug concentration and dose-dependent effect was observed. Fusion protein 15 has the same blocking capacity as fusion protein 9. Example test 4 Detection of binding affinity and in vitro kinetics using Biacore The affinity of the test molecule for human or murine PD-L1 protein TGF-βI or human PD-L1 was determined using Biacore T200 (GE). The experimental procedure is described as follows: A certain amount of PD-L1 / TGF-β trap was captured using protein chip A, and human or murine TGF-βI (8915LC, CST) or human PD-L1 (Sino Biological) was then flowed across the chip surface. The reaction signal was detected in real time using Biacore to obtain association and dissociation curves. The biochip was washed and regenerated with glycine-hydroxybutyric acid (pH 1.5, GE). The buffer solution used in the experiment was HBS-EP buffer (GE). The experimental data were fitted to the Langmuir (1:1) model using BIAevaluation software version 4.1 (GE), and the affinity values ​​are shown in Table 3. Table 3: Affinity of the fusion proteins of the present description to human TGF-βI or PD-L1 QLncnn / Lznz / E / Yi in vitro Fusion protein* Affinity sample ka (1 / Ms) kd (1 / s) KD (M) Human TGF-βI fusion protein 9 L73E7 7.28E-4 4.22E-11 Fusion protein 15 2.69E7 6.08E-4 2.26E-11 TGF-βI fusion protein 9 of 4.33E7 L33E-3 3.07E-11 Murine fusion protein 15 3.57E7 1.22E-3 3.42E-11 Human PD-L1 fusion protein 9 1.97E6 1.24E-4 6.31E-11 Fusion protein 15 2.00E6 1.24E-4 6.10E-11 * The shape of the fusion protein is shown in Table 2. QLncnn / Lznz / E / Yi The fusion protein binding activity is shown in Table 3. The results indicate that fusion protein 9 and fusion protein 15 of the present description have an extremely high affinity for human, murine TGF-βI and human PD-L1. Example test 5 SMAD3 reporter gene inhibition assay 1. Purpose of the test: In this experiment, the Smad3 binding element (SBE) with luciferase reporter gene was expressed in HepG2 cells to study the inhibitory effect of the PD-Ll / TGF-β trap on TGF-βI-induced Smad3 activation, and the PD-Ll / TGF-β trap activity in vitro was assessed according to the IC50 value. 2. Test sample: fusion protein 9, positive control (FP17022). 3. Testing Process HepG2 cells were cultured in complete MEM medium (GE, SH30243.01) comprising 10% FBS and subcultured every 3 days. On the first day of the experiment, 25,000 cells per well were inoculated into 96-well plates (Corning, 3903) and cultured at 37 °C, 5% CCl₂ for 24 hours. The following day, the medium in the cell culture plates was discarded, and 100 ng of 3TP-Lux plasmid was transfected per well. The cells were further cultured at 37 °C, 5% CO₂ for 24 hours. Six hours before the addition of the test sample, the complete medium in the 96-well plate was discarded, and 80 pL of incomplete medium (MEM + FBS ± 0.5%) was added to each well. After 6 hours, 10 pL of human TGF-βI solution (R&D, 240-B-010) prepared in incomplete medium (final concentration of 2 ng / mL) and 10 pL of the test sample (final concentration is 500, 50, 5, 0.5, 0.05, 0.005, 0) were added.0.005 and 0 nM), human TGF-βI solvent was used as a control and cells were cultured at 37 °C, 5% CO2 for an additional 18 h. Then, 100 pL of the ONE-Glo™ luciferase assay system of prepared luciferase substrate (Promega, E6110) was added to each well and incubated at room temperature for 10 minutes in the dark, and the luminescent signal value was then read using a Victor 3 multi-plate reader (Perkin Elmer). The IC50 value of the test sample was obtained by calculation using Graphpad Prism 5.0 data software. Figure 6 showed that fusion protein 9 inhibited TGFp-induced pSMAD3 reporter activity in a dose-dependent manner and had an IC50 efficacy (concentration required to inhibit 50% of maximum activity) comparable to that of the positive control FP 17022. PD-L1 antibody assay results showed no inhibitory effect (IC50 > 500 nM). Example test 6 In vitro detection of IFNy secretion by PBMCs due to tuberculin (TB) stimulation 1. Test objective To investigate T lymphocyte activation by PD-Ll / TGF-β trap, human peripheral blood mononuclear cells (PBMCs) were collected and purified and stimulated in vitro with tuberculin (TB) for 5 days to detect the level of cytokine IENG secretion. 2. Test sample: Human IgG; ©PD-L1 Antibody; ©·!Fusion protein 9; ® Control 1 (20T-Fc): ECD (20-136)-Fc; '©PD-L1+Control 1 Antibody (20T-Fc). 3. Testing Process Twenty percent tuberculin was added to 15 mL of freshly isolated and purified PBMCs (approximately 3 x 10⁷ cells / mL), and the culture was incubated for 5 days at 37 °C, 5% CO₂. On day 6, the cultured cells were harvested and centrifuged, washed once with PBS, and resuspended in fresh medium with the density adjusted to 1 x 10⁶ cells / mL. Ninety percent of the resuspended cells were added to a 96-well plate. Ten percent per well of different antibody concentrations was added separately to the corresponding wells of the 96-well cell culture plate, and ten percent PBS was added to the control and control groups, respectively. The cell culture plate was then incubated for three days at 37 °C, 5% CO₂. The cell culture plate was removed and the supernatant from each well was taken after centrifugation (4000 rpm, 10 min).After a 10-fold dilution, IFN-γ secretion was detected by ELISA (Human IFN-γ Detection Kit, NEOBIOSCIENCE, EHC 102g.96), according to the reagent instructions for specific operations. As shown in Table 4, all PD-L1 / TGF-β trap fusion protein samples were able to enhance IFN-γ cytokine secretion by activated T lymphocytes, and there was a drug concentration dose effect. q Lncnn / Lznz / E / Yii Table 4. The result of IFN-γ cytokine secretion EC50 Antibody (nM) Maximum IEγ Secretion (pg / mL) Minimum IEγ Secretion (pg / mL) Number of times (IEγ secretion) PD-L1 Antibody 0.05 2684 737 3.6 Fusion protein 9 0.12 3422 638 5.4 Control l(20T-Fc) >50 780 490 1.6 PD-L1 antibody + control 1 0.054 2879 746 3.9 Human IgG >50 375 298 1.2 Blank control / 536 536 1 4. Result QLncnn / Lznz / E / Yi As shown in Figure 7 and Table 4, fusion protein 9 was able to enhance the activated T lymphocyte to secrete the cytokine IFN-γ in a dose-dependent manner and had a more pronounced activation effect than the antibody PD-L1 and 20T-FC. Example test 7 Pharmacokinetic evaluation Three female SD rats were purchased from Jie Si Jie Laboratory Animal Co., Ltd. and kept on a 12 / 12 hour light / dark cycle (temperature 24±3°C, relative humidity 50-60%). The rats had free access to water and food. On the day of the experiment, the SD rats were injected into the cauda vein with fusion protein at a dose of 6 mg / kg and an injection volume of 5 mL / kg. Blood was drawn at the following time points: 15 min, 7 h (day 1), 24 h (day 2), day 3, day 4, day 60, day 8, day 10, and day 15 post-administration. 200 pL of blood (equivalent to 100 pL of serum) were drawn from the rat fundus vein. The blood sample was incubated at room temperature for 30 min to allow agglutination and then centrifuged at 10,000 g for 10 min at 4 °C. The supernatant was collected and immediately stored at -80 °C. The concentration of the fusion protein in the serum was quantified by ELISA. The quantification process is described as follows: a. The 96-well plates were coated with 100 pL / well of human PD-Ll-His at a concentration of 2 pg / mL, overnight at 4 °C. b. Wash 4 times with 250 pL of 1 xPBST, then 250 pL of 5% milk PBS was added to block at 37 °C for 3 hours. c. Washed 4 times with 250 pL of 1 xPBST, 100 pL of gradient-diluted serum sample was added and incubated at 37 °C for 1 hour, with sinriendo fusion protein 9 as a positive control. d. Wash 5 times with 250 pL 1 xPBST. e. 100 pL / well of biotinylated human anti-TGF-βRII antibody (I + D) was added and incubated for 1 hour at 37 °C. f. Wash 5 times with 250 pL 1 xPBST. g. 100 pL / well of TMB was added, incubated for 10 minutes at room temperature and the reaction was stopped by adding 100 pL of 1 M H2SO4. h. The absorbance at 450 nm was quantified on a microplate reader and the data were analyzed using Graphpad Prism 5. q Lncnn / Lznz / E / Yii Table 5: T 1 / 2 of fusion protein in SD rat Test drug Administration method Tl / 2 (Mean) Fusion protein 9 IV (6 mg / kg) 236±10 The results of the PK analysis indicated that the half-life of the fusion protein 9 of the present description in rats was approximately 236 h (9.8 days), see Table 5. Example Test 8 Effect of PD-L1 / TGF-β trap in murine subcutaneous xenograft in human breast cancer MDA-MB-231 The murine strain used in this experiment was a female NOD / SCID mouse (Cavens). The human peripheral blood mononuclear cells used in the experiment were extracted from freshly collected blood, and the extraction method was as follows: Heparin-anticoagulated venous blood was mixed with an equal volume of PBS containing 2% FBS, and after mixing, 25 mL of the diluted blood was slowly added to a centrifuge tube containing 15 mL of lymphocyte separation solution and centrifuged at 1200 g for 10 minutes at room temperature. The lymphocyte layer was pipetted into another centrifuge tube; the cells were washed with PBS and centrifuged at 300 g for 8 minutes at room temperature.After repeating once, the cells were resuspended in RPMI-1640 medium containing 10% FBS, and the cells were added to a 6-well plate pre-coated with CD3 antibody (OKT3, 40 ng / mL) at 2*106 cells / well (2 mL), and then placed in an incubator at 37°C for 4 days. Test sample: :i:blank witness: PBS; fusion protein 9: 4.8mpk; fusion protein 9:24mpk; @ PD-L1 antibody: 4mpk; PD-L1 antibody: 20mpk; @ PD-L1 antibody 4mpk + Control 1 (20T-Fc) 2.14mpk; CZ) Control 1 (20T-Fc): 2.14mpk. MDA-MB-231 cells were resuspended in serum-free RPMI-1640 medium and mixed with an equal volume of Matrigel. 100 pL (2.3 × 10⁶) was inoculated subcutaneously into the right flank of NOD / SCID mice. Eleven days later, animals with large or smaller tumors were excluded, and the mice were randomized into groups of nine animals each. 60 pL of stimulated 5 × 10⁵ PBMCs were injected into the tumor tissues, and the remaining PBMCs were further cultured without stimulation. One week later, 100 pL of 5 × 10⁶ PBMCs were injected intraperitoneally into tumor-bearing mice as the first round of injection. Over the course of the experiment, two and a half rounds, for a total of five PBMC injections, were administered. On the day of the first intratumoral injection, intraperitoneal administration was performed three times a week for a total of 14 administrations. The dosage regimen is shown in Table 6.Tumor volume and body weight were measured twice weekly. The experimental results are shown in Table 7. At the end of the experiment, the tumor-bearing mice were euthanized, and the tumor was removed and weighed. QLncnn / Lznz / B / Yii Table 6: Grouping and administration of tests Group Dosage Administration: Ϊ) Blank control: PBS 0 Fusion protein 9- 4.8mpk 4.8 mg / kg Fusion protein 9- 24mpk 24mg / kg Φ. PD-L1 antibody- 4mpk 4mg / kg PD-L1 antibody - 20mpk 20mg / kg @ PD-L1 antibody - 4mpk+control 1- 2.14mpk 4 mg / kg +2.14 mg / kg Φ Control 1- 2.14mpk 2.14mg / kg Table 7: Effect of fusion protein 9 on murine subcutaneous xenograft of MDA-MB-231 Group Day 0 Day 25 Day 32 Day 33 Mean± SEM Mean± SEM 0 / / 0 TGI Mean± SEM %TGI Mean± SEM P (vs PBS) (V mm3) (V mm3) (V mm3) (TW g) (TW) kU Blank control: PBS 62.5+2.9 623.4+ 43.3 - 941.1+ 54.9 - 0.859+ 0.063 - Fusion protein 9- 4.8mpk 62.6+3.5 414.6± γη 1*** 37.24 0 / / 0 618.9+ 2g 7*** 36.68 0 / / 0 0.454+ 0.025*** 2.06E- 05 Fusion protein 9- 24mpk 62.7+3.3 329.8+ 22.5*** 52.38 0 / / 0 495.3+ 42.6*** 50.76 0 / / 0 0.367+ 0.026*** 2.20E- 06 PD-L1 Antibody - 63.1+3.5 454.4+ 30.24 722.8+ 24.91 0.592+ 0.0050 4mpk 40.8* 0 / / 0 65.8* 0 / / 0 0.052** ©PD-L1 Antibody 20mpk 62.6±3.3 466.4± 17.2** 28.01 0 / / 0 741.8± 32.9** 22.70 0 / / 0 0.650± 0.033** 0.0100 Φ) PD-L1 Antibody 4mpk+control 1- 2.14mpk 62.6±3.3 447.5± 29.6** 31.38 % 669.2± 45.3** 30.96 % 0.566± 0.039** 0.0012 •7) Control 1-2.14mpk 60.7±3.3 601.5± 30.9 3.58% 861.7± 34.2 8.83% 0.652± 0.041* 0.0178 QLncnn / Lznz / E / Yi Day 0: time to first administration; *p<0.05 * p<0.01 * p<0.001, compared to PBS by Student's t test. Figure 8 shows the results. The antibody fusion protein 9 (4.8 mg / kg, 24 mg / kg) significantly inhibited the growth of the murine subcutaneous xenograft of human breast cancer MDA-MB-231. There was a dose-dependent relationship between high and low doses, and it was superior to the reference drug PD-L1 antibody (4 mg / kg, 20 mg / kg), the control molecule TGFβKII 20T-FC (2.14 mg / kg), and the combination group (PD-L1 antibody - 4 mg / kg + 20T-FC - 2.14 mg / kg) at equivalent molar doses, respectively. Each dose of fusion protein 9 maintained the desired antitumor effect from day 14 post-administration. Compared to the PD-L1 antibody, 20T-FC, fusion protein 9 at the high dose had a clear advantage (p < 0.5). Within 25 days of administration, the antitumor effect of each antibody reached an optimal level.The antitumor rates for the low-dose and high-dose fusion protein 9 and PDL-f antibody groups, and the combined group, were 37.24%, 52.38%, 30.24%, 28.01%, and 31.38%, respectively. At 320 days post-administration, the antitumor effect of fusion protein 9 remained highly significant. The percentage of gastrointestinal (GIG) reduction in the low-dose and high-dose groups was 36.68% and 50.76%, respectively, and tumor volume was statistically different compared to the control group (p<0.05). Example test 9 Physical stability of the PD-LÍ / TGF-β trap This test example was used to detect the stability of fusion protein 9 and fusion protein 15. Differential scanning calorimetry (DSC) was used to detect the thermal stability of different antibodies, and their stability was compared in different buffer systems. The buffer systems included 10 mM acetate / 135 mM NaCl (pH 5.5) and 10 mM acetate / 9% trehalose (pH 5.5). The sample was dissolved in the appropriate buffers and the concentration was controlled at approximately 50 mg / mL. Detection was performed using MicroCal* VP-Capillary DSC (Malvem). Before testing, each sample and buffer blank was degassed for 1–2 min using a vacuum degassing device. Each well of the plate was loaded with 400 pL of sample or buffer blank (the loading amount was 300 pL). Two pairs of well plates containing 14% Decon 90 and ddH₂O, respectively, were then prepared for washing. The sample was loaded onto the plate, and the plate was sealed with a plastic cover. The scan began at 25 °C and ended at 100 °C, with a scan rate of 60 °C / h. The results are shown in Table 8, indicating that both fusion protein 9 and fusion protein 15 exhibited good thermal stability in these two test systems. QLncnn / Lznz / B / Yi Table 8. Thermostability test Sample Buffer Start-Tm (°C) TM (°C) 10 mM Acetate Protein / 135 mM NaCl 57.99 66.33 fusion 9 10 mM Acetate / 9% trehalose 58.64 67.83 10 mM Acetate Protein / 135 mM NaCl 57.33 66.17 fusion 15 Acetate 10 mM / 9% trehalose 57.41 67.44 Periodic stability at a given concentration was investigated by monitoring purity using SEC-HPLC under exemplary conditions. For instance, the sample concentration was controlled at approximately 50 mg / mL in 10 mM acetate / 135 mM NaCl (pH 5.5), and stability was compared under conditions such as five freeze-thaw cycles at -80 °C versus after storage at 40 °C for one month. The Xbridge BEH SEC 200A protein HPLC column (Aguas) was used for detection. The results are shown in Table 9, and these two fusion proteins exhibited good stability. Table 9. Stability fusion protein 9(Δ%) fusion protein 15(Δ%) 40°C 3.39% 1.8% -80°C freeze-thaw 1.44% 1.39% Note: Δ% indicates the rate of change. Example test 10 Chemical stability of the fusion protein Deamidation is a common chemical modification that will influence antibody stability at a later stage. It is generally chosen to avoid or reduce the highly deamidated modification of some amino acids in the CDR regions as much as possible through mutation. 1600 µg of the antibody to be analyzed were dissolved in 200 µA of 10 mM / 135 mM NaCl acetate (pH 5.5) and incubated at 40 °C. Samples were taken on days 0, 14, and 28 for the enzymatic hydrolysis assay. 100 pg of each sample taken at different time points were dissolved in 100 µA of 0.2 M HisHC1, 8 M Gua-HCl solution, pH 6.0; 3 pL of 0.1 g / mL of TDT were added, and the sample was then incubated in a water bath at 50 °C for 1 hour. The sample was then ultrafiltered twice with 0.02 M His-HCl (pH 6.0) and digested overnight at 37 °C in a water bath by adding 3 pL of 0.25 mg / mL trypsin.The deamidation modification was examined using an Agilent 6530 Q-TOF LC-MS, and the results were shown in Table 10 below. QLncnn / Lznz / E / Yi Table 10. Deamidated modification Sample Heavy Chain Modification Site Day 0 Day 14 Day 28 Fusion Protein 9 Heavy Chain N314 2.38% 2.28% 2.45% N324 0.20% 3.60% 7.88% Fusion Protein 15 Heavy Chain N314 2.87% 2.86% 2.87% N324 0.00% 3.61% 7.93% Note: N represents detectable modified asparagine, and the number represents the position on the light or heavy chain from the N-terminal end. The percentage content represents the proportion of deamidation modification detected by LC-MS to the signal of all peptides at that site. The mass spectrometry results showed that the two fusion proteins have no obvious deamidation modification sites, suggesting that the fusion proteins have good chemical stability. Example of Preparations Examples of preparation processes for pharmaceutical composition of fusion proteins (preparation) The first step: A certain amount of purified TGF-β receptor fusion protein stock solution was taken and the solvent was replaced (preferably by ultrafiltration) using a protein-free buffer (such as 10 mM sodium citrate-citric acid buffer, pH 6.2) by passing it through an ultrafiltration membrane for at least six times the volume. The protein was then concentrated to approximately 70 mg / mL. A specific volume of sucrose stock solution was added and mixed to achieve a final sucrose concentration of 80 mg / mL. A specific volume of Tween-80 stock solution was added and mixed to achieve a final Tween-80 concentration of 0.4 mg / mL. 10 mM citrate buffer, pH 6.2, was added to reach a specified volume to obtain a protein concentration of 50 mg / mL (other preparations to be analyzed or stable preparations were prepared according to similar steps). After filtration, the product was sampled for sterility testing as a control medium. The stock solution was passed through a 0.22 μM PVDF filter, and the filtrate was collected. The second stage: the fill volume was adjusted to 6.3 mL, the filtrate was loaded into a 6 mL vial, which was then capped with a stopper, and samples were taken at the beginning, in the middle and at the end of the fill to detect the difference in fill volume, due to the purpose of a medium control. The third step: the capping machine was started; the aluminum lids were capped. The fourth step: a visual inspection was performed to confirm that the product had no defects such as inaccurate filling. Labels were printed and affixed to vials; cardboard labels were printed, boxes were folded, loaded with vials, and labeled. Example of preparation 1. Detection of the pH value for the buffer system of TGF-β receptor fusion protein preparations TGF-β receptor fusion protein preparations (fusion protein 9) were prepared using the following buffers, with a protein concentration of 50 mg / mL: 1) Acetic acid-histidinalO mM, pH 5.0; 2) Acetic acid-histidinalO mM, pH 6.0; 3) Acetic acid-histidinalO mM, pH 6.5; 4) 10 mM disodium monobasic phosphate-hydrogen phosphate, pH 7.0; 5) 10 mM of monobasic sodium-disodium phosphate, pH 7.5. Each preparation was filtered and added at 1.2 mL / vial to a 2 mL injection vial made of neutral borosilicate glass. The injection vial was fitted with a stopper, capped, and sealed. Samples were taken and subjected to high temperature (40 °C) and shaking experiments. The experimental results are shown in Table 11. The results show that TGF-β receptor fusion proteins have better stability at pH 6.0–6.5. Table 11. Screening results of the forced degradation experiment QLncnn / Lznz / E / Yi No. Time Interval Appearance SEC (%) added monomer fragment 1 T0 pronounced opalescence 2.0 97.1 LO with stirring D7 cloudy 3.5 94.8 1.7 40 °C M2 clear and colorless 8.1 87.1 4.7 2 T0 light blue opalescence 2.7 97.0 0.3 with stirring D7 cloudy 3.0 96.2 0.9 40 °C M2 transparent and colorless 5.9 91.1 3.0 3 T0 transparent and colorless 2.7 96.9 0.3 with stirring D7 large amount of flocculent precipitate 3.0 95.7 1.3 40 °C M2 transparent and colorless 5.0 91.7 3.3 4 T0 fine and colorless particles 3.1 96.5 0.5 with stirring D7 large amount of flocculent precipitate 3.6 95.3 1.2 40 °C M2 transparent and colorless 4.5 71.5 23.9 5 T0 fine and colorless particles 3.2 96.5 0.4 with stirring D7 large amount of flocculent precipitate 3.7 95.0 1.3 40 °C M2 transparent and colorless 4.9 60.8 34.3 q Lncnn / Lznz / E / Yi Note: The shaking condition was: DI: 130 rpm, D2: 200 rpm, D3-D7: 300 rpm; D means day, T means time, and M means month. Example of preparation 2. Detection of the buffer system for TGF-β receptor fusion protein preparations TGF-β receptor fusion protein preparations (fusion protein 9) were prepared using the following buffers, with a protein concentration of 50 mg / mL: 1) 10 mM sodium succinic acid succinate, pH 6.0; 2) Citric acid-sodium citrate 10 mM, pH 6.0; 3) Citric acid-sodium citrate 10 mM, pH 6.5; 4) 10 mM disodium monobasic phosphate-hydrogen phosphate, pH 6.5; 5) 10 mM histidine-hydrochloride, pH 6.5. Each preparation was filtered and added at 1.2 mL / vial to a 2 mL injection vial made of neutral borosilicate glass. The injection vial was capped and sealed. Samples were taken for the shaking experiment (at 25 °C, 300 rpm). The experimental results are shown in Table 12. The results show that a large number of small particles were observed in the sodium phosphate-sodium phosphate-disodium hydrogen phosphate cluster on the sixth day under shaking, with aggregates reaching 1.8% as detected by SEG. However, only occasional minute particles were observed in other clusters. It can be observed that the stability of the TGF-β receptor fusion protein in citric acid, histidine, and succinate buffer systems is better than that in phosphate buffer systems. Table 12. Results of the selection experiment for the buffer system and pH value No. Time Interval Appearance SEC (%) Added Monomer Fragment 0 1 DO transparent and colorless 1.6 98.1 0.3 with agitation D6 minute particles occasionally 1.7 97.7 0.6 2 DO transparent and colorless 1.5 98.0 0.5 with agitation D6 minute particles occasionally 1.5 97.8 0.7 3 DO transparent and colorless 1.6 98.0 0.4 with agitation D6 minute particles occasionally 1.7 97.7 0.6 4 DO transparent and colorless 1.6 98.0 0.4 with agitation D6 large quantity of minute particles 1.8 97.6 0.7 5 DO transparent and colorless 1.5 98.0 0.5 with agitation D6 minute particles occasionally 1.6 97.8 0.7 Note: D represents the days. QLncnn / Lznz / E / Yi Example of preparation 3. Additional detection of the buffer system for TGF-β receptor fusion protein preparation A pH 6.2 buffer comprising 10 mM histidine-hydrochloride or 10 mM citric acid-sodium citrate was used to prepare a preparation comprising 80 mg / mL sucrose, 0.4 mg / mL polysorbate 80, TGF-β receptor fusion protein (fusion protein 9) at a concentration of 50 mg / mL. Each preparation was filtered and added to 1.2 mL / vial in a 2 mL capacity injection vial made of neutral borosilicate glass. The injection vial was supplied with a stopper, capped, and sealed. Samples were stored at 25 °C for stability analysis, 6-month EC-SDS detection, and non-reducing O. The experimental results were shown in Table 13. The results show that the citric acid-sodium citrate system is better than the histidine-hydrochloride system (M6 SEG aggregate: 1.8% vs. 2.2%; non-reducing CE-SDS: 94.5% vs. 92.2%); therefore, the citric acid system can be selected as the buffer system for the TGF-β receptor fusion protein. Table 13. Results of the accelerated stability test for the detection of the damping system at °C QLncnn / Lznz / B / Yi Buffer System Time Appearance SEC (%) CE-SDS non-reducing (%) aggregate monomer fragment citrate buffer system T0 translucent 1.6 97.6 0.7 91.2 D24 translucent 1.6 97.7 0.7 90.4 M2 translucent 1.7 97.5 0.8 N / A M3 translucent 1.8 97.9 0.3 96.2 M6 large amount of turbid particles 1.8 97.9 0.4 94.5 histidine salt buffer system T0 translucent 1.5 97.7 0.8 91.3 D24 translucent 1.6 97.4 1.1 90.4 M2 translucent 1.7 97.5 0.8 N / A M3 translucent 1.8 97.7 0.5 95.4 M6 large quantity of turbid particles 2.2 97.3 0.5 92.2 Note: T stands for time; D stands for day; M stands for month. Example of preparation 4. Detection of stabilizers for TGF-β receptor fusion protein preparations TGF-β receptor fusion protein preparations (fusion protein 9) were prepared using the following different saccharide buffers, with a protein concentration of 50 mg / mL: 1) 10 mM citric acid-sodium citrate, 80 mg / mL sucrose, pH 6.2; 2) 10 mM citric acid-sodium citrate, 80 mg / mL α,α-trehalose dihydrate, pH 6.2. Each preparation was filtered and added at 1.2 mL / vial to a 2 mL capacity injection vial made of neutral borosilicate glass. The injection vial was fitted with a stopper, capped, and sealed. Samples were taken for long-term storage experiments at 25 °C at room temperature and at 2–8 °C at low temperature. The experimental results are shown in Table 14. The results show that sucrose and trehalose have similar effects on the stability of the TGF-β receptor fusion protein (fusion protein 9). Sucrose was selected as the stabilizer for the TGF-β receptor fusion protein (fusion protein 9). When the sucrose concentration is 80 mg / mL, the osmotic pressure is approximately 300 mL / kg, which is close to isotonic; therefore, the sucrose concentration can be 80 mg / mL. QLncnn / Lznz / E / Yii Table 14. Results of screening experiments for saccharide types No. Time Interval Appearance SEC (%) EC-SDS non-reducing (%) aggregate 0 monomer 0 fragment 0 1 T0 transparent and colorless 1.6 97.6 0.7 91.2 25°C M6 large amount of cloudy particles 1.8 97.9 0.4 94.5 2-8°C M6 transparent and colorless 1.7 98.1 0.1 96.8 2 T0 translucent 1.6 97.7 0.7 91.6 25°C M6 considerable cloudy particles 1.9 97.8 0.3 94.1 2-8°C M6 transparent and colorless 1.8 97.8 0.4 97.5 Note: T stands for time, and M stands for month. Example of preparation 5. Detection of surfactants for TGF-β receptor fusion protein preparations TGF-β receptor fusion protein preparations (fusion protein 9) were prepared using the following buffers of different types of surfactants at different concentrations, with a protein concentration of 50 mg / mL: 1) 10 mM histidine hydrochloride, 0.1 mg / mL polysorbate 20, pH 6.2; 2) 10 mM histidine hydrochloride, 0.2 mg / mL polysorbate 20, pH 6.2; 3) 10 mM histidine hydrochloride, 0.4 mg / mL polysorbate 20, pH 6.2; 4) 10 mM histidine hydrochloride, 0.6 mg / mL polysorbate 20, pH 6.2; 5) 10 mM histidine hydrochloride, 0.8 mg / mL polysorbate 20, pH 6.2; 6) 10 mM histidine hydrochloride, 0.1 mg / mL polysorbate 80, pH 6.2; 7) 10 mM histidine hydrochloride, 0.2 mg / mL polysorbate 80, pH 6.2; 8) 10 mM histidine hydrochloride, 0.4 mg / mL polysorbate 80, pH 6.2; 9) 10 mM histidine hydrochloride, 0.6 mg / mL polysorbate 80, pH 6.2; 10) 10 mM histidine-hydrochloride, 0.8 mg / mL polysorbate 80, pH 6.2. Each preparation was filtered, and 0.5 mL of the preparation was injected into 50 mL of saline injection or 5% glucose injection solution to achieve a protein concentration of 0.5 mg / mL after dilution. Sample stability was observed after dilution. The results of the experiment are shown in Table 15. The results show that when the polysorbate 20 concentration in the preparation reached more than 0.2 mg / mL, the insoluble particles decreased significantly after dilution. Regarding polysorbate 80, the insoluble particles produced due to sodium chloride dilution decreased with increasing polysorbate 80 concentration. When polysorbate 80 reached 0.4 mg / mL or more, particles larger than 10 μm were reduced to fewer than 10 particles / mL. Table 15. Results of the polysorbate detection experiment - dilution and stirring QLncnn / Lznz / B / Yi Number of insoluble particles after dilution (particles / mL) 0.9% NaCl 5% Glucose 2pm 10pm 25pm 2pm 10pm 25pm 1 1454 18 0 318 10 0 2 48 1 0 104 2 0 3 65 2 0 177 3 0 4 26 1 0 102 1 0 5 112 3 0 82 2 0 6 568 36 1 46 1 0 7 668 14 0 30 1 0 8 135 3 0 92 4 0 9 623 8 0 30 1 0 10 113 2 0 97 6 0 Example of preparation 6. Additional detection of surfactants for TGF-β receptor fusion protein preparations TGF-β receptor fusion protein preparations (fusion protein 9) were prepared using the following buffers of different types of surfactants, with a protein concentration of 50 mg / mL: 1) 10 mM citric acid-sodium citrate, 0.4 mg / mL polysorbate 80, pH 6.2; 2) 10 mM citric acid-sodium citrate, 0.6 mg / mL polysorbate 20, pH 6.2. Each preparation was filtered and added at 1.2 mL / vial to a 2 mL injection vial made of neutral borosilicate glass. The injection vial was fitted with a stopper, capped, and sealed. Samples were taken for long-term storage experiments at a low temperature of 2–8 °C. The experimental results are shown in Table 16. The results indicate that polysorbate has a better stabilizing effect on the TGF-β receptor fusion protein (fusion protein 9). Therefore, polysorbate 80 was selected as the surfactant for the TGF-β receptor fusion protein (fusion protein 9). Table 16. Results of the long-term stability experiment at 2-8 °C for the detection of polysorbate QLncnn / Lznz / E / Yi No. Time Interval Appearance SEC (%) EC-SD non-reducing (%) aggregate monomer fragment 0 1 T0 transparent and colorless 1.6 97.6 0.7 91.2 D45 transparent and colorless 1.7 97.4 1.0 N / A M3 transparent and colorless 1.8 98.0 0.3 97.4 M6 transparent and colorless 1.7 98.1 0.1 96.8 2 T0 transparent and colorless 1.6 97.8 0.6 91.7 D45 large amount of particles 1.7 97.5 0.8 N / A M3 large amount of particles 1.8 97.9 0.3 97.5 M6 large amount of particles and turbidity 1.7 97.8 0.4 96.7 Note: T stands for time, D stands for day, and M stands for month. Example of preparation 7. Filter membrane compatibility test for TGF-β receptor fusion protein preparations TGF-β receptor fusion protein (fusion protein 9) was formulated at 50 mg / mL in 10 mM citric acid-sodium citrate buffer, 80 mg / mL sucrose, 0.4 mg / mL polysorbate 80, pH 6.2. The preparations were passed through a 0.22 pm PES filter membrane and a PVDF filter membrane, respectively, and samples were taken at the beginning, middle, and end of the test. The experimental results were shown in Table 17. The analysis of protein content, appearance, and purity shows that the TGF-β receptor fusion protein (fusion protein 9) was stable during contact with the filter membrane, and the preparation was compatible with PES and PVDF filter membranes. QLncnn / Lznz / E / Yi Table 17. Results of the filter membrane compatibility tests Filter Membrane Protein Concentration mg / mL SEC % EC-SDS Non-reducing (%) Polysorbate Content mg / mL Added Monomer Fragment T0 50.8 0.8 98.9 0.3 98.1 0.46 PES, Main Filtrate 51.4 0.9 98.9 0.2 98.0 0.46 PES, Middle Filtrate 49.8 0.9 98.9 0.3 98.0 0.46 PES, Final Filtrate 50.0 0.9 98.9 0.2 98.0 0.46 PVDF, Main Filtrate 49.6 0.9 98.7 0.4 97.9 0.46 PVDF, Middle Filtrate 50.2 0.9 98.8 0.3 98.0 0.46 PVDF, Final Filtrate 50.0 0.9 98.8 0.3 97.9 0.45 Note: ' represents time. Example of preparation 8. Lyophilization of TGFβ receptor fusion protein preparation The TGF-β receptor fusion protein preparation (fusion protein 9) was prepared comprising a concentration of 50 mg / mL of TGF-β receptor fusion protein (fusion protein 9), 80 mg / mL of sucrose, and 0.4 mg / mL of polysorbate 80 with a pH 6.2 buffer comprising 10 mM citric acid-sodium citrate. The antibody was added at 6.3 mL / vial to a 20 mL vial and placed in a deep freezer for lyophilization. The freeze-drying process includes pre-freezing, primary drying, and secondary drying. Once the freeze-drying process was complete, the vial was vacuum-sealed. The samples were reconstituted, and a pre- and post-freeze-drying comparison was performed. The results show that the reconstituted solution maintains a favorable performance similar to that of the prepared solution. Table 18. Lyophilization stages of the preparations Freeze-drying parameters Temperature setting (°C) Vacuum level (mBar) Pre-freezing 5 N / A -45 N / A Primary drying -27 0.1 Secondary drying 25 0.1 25 0.01 QLncnn / Lznz / E / Yi Example of preparation 9. Other optional preparation compositions In addition, this description provides other preparations of pharmaceutical preparations of TGF-β receptor fusion protein (fusion protein 9): (1) 70 mg / mL of fusion protein 9, 75 mg / mL of sucrose, 0.4 mg / mL of polysorbate 80 and 20 mM of citric acid-sodium citrate buffer, the final pH is 6.4; (2) 80 mg / mL of fusion protein 9, 85 mg / mL of sucrose, 0.5 mg / mL of polysorbate 80 and 15 mM of citric acid-sodium citrate buffer, the final pH is 6.2; (3) 60 mg / mL of fusion protein 9, 90 mg / mL of sucrose, 0.6 mg / mL of polysorbate 80 and 5 mM of citric acid-sodium citrate buffer, the final pH is 6.2; (4) 30 mg / mL of fusion protein 9, 60 mg / mL of sucrose, 0.3 mg / mL of polysorbate 80 and 30 mM of citric acid-sodium citrate buffer, the final pH is 6.3; (5) 90 mg / mL of fusion protein 9, 95 mg / mL of sucrose, 0.2 mg / mL of polysorbate 80 and 10 mM of citric acid-sodium citrate buffer, the final pH is 6.0; (6) 100 mg / mL of fusion protein 9, 70 mg / mL of sucrose, 0.1 mg / mL of polysorbate 80 and 25 mM of citric acid-sodium citrate buffer, the final pH is 6.5; (7) 50 mg / mL of fusion protein 9, 80 mg / mL of sucrose, 0.4 mg / mL of polysorbate 80 and 10 mM of citric acid-sodium citrate buffer, the final pH is 7.0; (8) 50 mg / mL of fusion protein 9, 80 mg / mL of sucrose, 0.4 mg / mL of polysorbate 80 and 10 mM of citric acid-sodium citrate buffer, the final pH is 7.5; (9) 50 mg / mL of fusion protein 9, 80 mg / mL of sucrose, 0.4 mg / mL of polysorbate 80 and 10 mM of citric acid-sodium citrate buffer, the final pH is 5.0; (10) 60 mg / mL of fusion protein 9, 70 mg / mL of sucrose, 0.5 mg / mL of polysorbate 80 and 15 mM of citric acid-sodium citrate buffer, the final pH is 5.5; (11) 40 mg / mL of fusion protein 9, 80 mg / mL of sucrose, 0.5 mg / mL of polysorbate 80 and 10 mM of citric acid-sodium citrate buffer, the final pH is 6.2; (12) 55 mg / mL of fusion protein 9, 75 mg / mL of sucrose, 0.3 mg / mL of polysorbate 80 and 5 mM of citric acid-sodium citrate buffer, the final pH is 6.0; (13) 65 mg / mL of fusion protein 9, 90 mg / mL of sucrose, 0.7 mg / mL of polysorbate 80 and 30 mM of citric acid-sodium citrate buffer, the final pH is 7.5; (14) 70 mg / mL of fusion protein 9, 75 mg / mL of sucrose, 0.8 mg / mL of polysorbate 80 and 30 mM of citric acid-sodium citrate buffer, the final pH is 7.0; (15) 50 mg / mL of fusion protein 9, 80 mg / mL of sucrose, 0.8 mg / mL of polysorbate 80 and 10 mM of citric acid-sodium citrate buffer, the final pH is 7.0. q Lncnn / Lznz / E / Yi

Claims

1. A pharmaceutical composition comprising: a TGF-β receptor fusion protein, and a buffer; wherein the buffer is selected from the group consisting of a histidine salt buffer, a succinate buffer, and a citrate buffer.

2. The pharmaceutical composition according to claim 1, wherein: the histidine salt buffer is a histidine-hydrochloric acid buffer, the succinate buffer is a succinic acid-sodium succinate buffer, the citrate buffer is a citric acid-sodium citrate buffer; preferably, the buffer is a citric acid-sodium citrate buffer.

3. The pharmaceutical composition according to claim 1 or 2, wherein the buffer concentration is from approximately 5mM to approximately 30mM, preferably from approximately 5mM to approximately 20mM, more preferably from approximately 10mM.

4. The pharmaceutical composition according to any of claims 1 to 3, wherein the concentration of the TGF-β receptor fusion protein is from approximately 0.5 mg / mL to approximately 100 mg / mL, preferably from approximately 30 mg / mL to approximately 70 mg / mL, more preferably from approximately 50 mg / mL.

5. The pharmaceutical composition according to any one of claims 1 to 4, wherein the pH of the pharmaceutical composition is from approximately 5.0 to approximately 7.5, preferably from approximately 6.0 to approximately 6.5, more preferably from approximately 6.

2.

6. The pharmaceutical composition according to any of claims 1 to 5, wherein: the pharmaceutical composition further comprises a saccharide, preferably the saccharide is selected from the group consisting of: a trehalose and a sucrose, more preferably the saccharide is a sucrose.

7. The pharmaceutical composition according to claim 6, wherein the concentration of the saccharide is from approximately 50 mg / mL to approximately 100 mg / mL, preferably from approximately 60 mg / mL to approximately 90 mg / mL, more preferably from approximately 80 mg / mL.

8. The pharmaceutical composition according to any one of claims 1 to 7, wherein: the pharmaceutical composition further comprises a surfactant, preferably a polysorbate, more preferably a polysorbate 80. q Lncnn / Lznz / E / Yii 9. The pharmaceutical composition according to claim 8, wherein the surfactant concentration is from approximately 0.1 mg / mL to approximately 0.8 mg / mL, preferably from approximately 0.4 mg / mL to approximately 0.8 mg / mL, more preferably from approximately 0.4 mg / mL.

10. The pharmaceutical composition according to any of claims 1 to 9, comprising: from approximately 0.5 mg / mL to approximately 100 mg / mL TGF-β receptor fusion protein, from approximately 5 mM to approximately 30 mM citrate buffer, from approximately 50 mg / mL to approximately 100 mg / mL sucrose, and from approximately 0.1 mg / mL to approximately 0.8 mg / mL polysorbate 80; preferably, the pH of the pharmaceutical composition is from approximately 5.0 to approximately 7.5; more preferably, the pH of the pharmaceutical composition is from approximately 6.0 to approximately 6.5; preferably, the pharmaceutical composition comprises: QLncnn / Lznz / B / Yi of approximately 30 to approximately 70 mg / mL of TGF-β receptor fusion protein, of approximately 5 to approximately 20 mM of citric acid-sodium citrate buffer, of approximately 60 to approximately 90 mg / mL of sucrose, and of approximately 0.4 to approximately 0.8 mg / mL of polysorbate 80; preferably, the pH of the pharmaceutical composition is from approximately 6.0 to approximately 6.5; more preferably, the pharmaceutical composition comprises: approximately 50 mg / mL of TGF-β receptor fusion protein, approximately 10 mM of citric acid-sodium citrate buffer, approximately 80 mg / mL of sucrose, and approximately 0.4 mg / mL of polysorbate 80; preferably, the pH of the pharmaceutical composition is from approximately 6.

2.

11. The pharmaceutical composition according to any of claims 1 to 10, wherein the TGF-β receptor fusion protein is shown as general formula (I): Ab-L-TGF-pRII ECD (I) wherein the ECD of TGF^RII is a truncated form of an extracellular region of TGF-β RII: Ab is a PD-L1 antibody or antigen-binding fragment thereof; L is a binding sequence.

12. The pharmaceutical composition according to claim 11, wherein the linking sequence is shown as (G4S)XG, wherein x is 3, 4, 5 or 6, preferably x is 4.

13. The pharmaceutical composition according to claim 11 or 12, wherein the truncated form of the extracellular region of TGF-βRII is an extracellular domain sequence of TGF-βRII with a deletion of at most 26 consecutive amino acid residues at the amino terminus; preferably, an extracellular domain sequence of TGF-βRII with a deletion of 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 consecutive amino acid residues at the amino terminus; more preferably, the TGF-βRII ECD sequence is shown as SEQ ID NO: 14, 15, 16 or 17; preferably, it is shown as SEQ ID NO:

15.

14. The pharmaceutical composition according to any one of claims 11 to 13, wherein the PD-L1 antibody or antigen-binding fragment thereof comprises: (A) HCDR1, HCDR2 and HCDR3 shown as SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively; and LCDR1, LCDR2 and LCDR3 shown as SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively; or (B) HCDR1, HCDR2 and HCDR3 shown as SEQ ID NO: 1, SEQ ID NO: 10 and SEQ ID NO: 3, respectively, and LCDR1, LCDR2 and LCDR3 shown as SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively.

15. The pharmaceutical composition according to any of claims 11 to 14, wherein the PD-L1 antibody or antigen-binding fragment thereof comprises: (C) a variable heavy chain region shown as SEQ ID NO:7 and a variable light chain region shown as SEQ ID NO: 8; oq Lncnn / Lznz / E / Yi (D) a variable heavy chain region shown as SEQ ID NO:9 and a variable light chain region shown as SEQ ID NO:

11.

16. The pharmaceutical composition according to any one of claims 11 to 15, wherein: the heavy chain amino acid sequence of the PD-L1 antibody is shown as SEQ ID NO: 12 or has at least 85% identity with the amino acid sequence shown as SEQ ID NO: 12; the light chain amino acid sequence of the PD-L1 antibody is shown as SEQ ID NO: 13 or has at least 85% identity with the amino acid sequence shown as SEQ ID NO:

13.

17. The pharmaceutical composition according to any of claims 11 to 16, wherein ECD TGF-βKIII is fused to the carboxyl terminus of the PD-L1 antibody heavy chain via a linker sequence; preferably, the TGF-β receptor fusion protein comprises: (E) a fusion peptide formed from the PD-L1 antibody heavy chain and ECD TGF-βKIII, the sequence of which is shown as SEQ ID NO:23 or has at least 85% identity with the sequence shown as SEQ ID NO:23, and wherein the PD-L1 antibody light chain has the sequence shown as SEQ ID NO:13 or has at least 85% identity with the sequence shown as SEQ ID NO:13;or (F) a fusion peptide formed from the PD-L1 antibody heavy chain and TOE-βKIII ECD, the sequence of which is shown as SEQ ID NO:24 or has at least 85% identity with the sequence shown as SEQ ID NO:24, and the PD-L1 antibody light chain, the sequence of which is shown as SEQ ID NO:13 or has at least 85% identity with the sequence shown as SEQ ID NO:13.; 18. A method for preparing the pharmaceutical composition according to any of claims 1 to 17, wherein the method comprises: a step for contacting the TGF-β receptor fusion protein with the buffer; preferably, the buffer is a citric acid-sodium citrate buffer, preferably the concentration of the buffer is from approximately 5mM to approximately 20mM, and the pH of the buffer is from approximately 6.0 to approximately 6.

5.

19. A lyophilized preparation comprising a TGF-β receptor fusion protein, obtained by lyophilizing the pharmaceutical composition according to any of claims 1 to 17.

20. A lyophilized preparation comprising a TGF-β receptor fusion protein, which can be reconstituted to form the pharmaceutical composition according to any of claims 1 to 17. QLncnn / Lznz / E / Yi 21. A reconstituted solution comprising a TGF-β receptor fusion protein, obtained by reconstituting the lyophilized preparation according to claim 19 or 20.

22. A manufactured article comprising one or more containers, wherein the container comprises: the pharmaceutical composition according to any of claims 1 to 17, or the lyophilized preparation comprising a TGF-β receptor fusion protein according to claim 19 or 20, or the reconstituted solution comprising a TGF-β receptor fusion protein according to claim 21.

23. The use of any selected from the following for the preparation of a medicament: the pharmaceutical composition according to any one of claims 1 to 17, or the lyophilized preparation comprising a TGF-β receptor fusion protein according to claim 19 or 20, or the reconstituted solution comprising a TGF-β receptor fusion protein according to claim 21, or the article manufactured according to claim 22; preferably, the medicament is used to treat or inhibit diseases or disorders related to the proliferation of tumor cells or metastasis of tumor cells; more preferably, the disease or disorders are a tumor;More preferably, diseases or disorders are selected from the group consisting of: cranial and cervical cancer, glioblastoma, glioma, nasopharyngeal carcinoma, thyroid cancer, lung cancer, myelomatic cancer, myelodysplastic syndrome, neuroendocrine cancer, lymphoma, leukemia, melanoma, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, dermatofibrosarcoma protuberans, Merkel cell carcinoma, sarcoma, mesothelioma, gastric cancer, liver cancer, pancreatic cancer, kidney cancer, bladder cancer, colorectal cancer, breast cancer, endometrial cancer, uterine cancer, cervical cancer, ovarian cancer, prostate cancer, and testicular cancer; lung cancer is selected from the group consisting of: small cell lung cancer and non-small cell lung cancer.