An anti-cd147 f(ab')2 antibody and its use in metabolic-related diseases

Abstract

The present application relates to the technical field of biopharmaceuticals, in particular to an anti-CD147 F(ab')2 antibody and its use in metabolic related diseases. The main technical solution of the present application is the use of the anti-CD147 F(ab')2 antibody in pharmacy; wherein the drug is a drug for preventing and / or treating metabolic related diseases. The present application first discovers that the anti-CD147 antibody can play a role in treating and improving metabolic diseases, first expands the indication of the CD147 antibody to the field of metabolic diseases, and adds a new target for the regulation of sugar and lipid metabolism.

Description

Technical Field

[0001] This invention relates to the field of biopharmaceutical technology, specifically to an anti-CD147 F(ab')2 antibody and its use in metabolic-related diseases. Background Technology

[0002] Obesity has become one of the most serious public health challenges globally. According to data from the World Obesity Federation, the global overweight and obese population continues to grow, and it is projected that the number of obese adults worldwide will exceed 1.1 billion by 2030. In China, the overweight rate among adults is 34.3%, and the obesity rate is 16.4%, making China the country with the largest overweight and obese population globally. The prevalence of type 2 diabetes continues to rise, reaching 11.2% among Chinese adults, with over 140 million patients, the vast majority of whom have type 2 diabetes. More than 60% of type 2 diabetes patients are also overweight or obese. Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease globally, with a prevalence of nearly 30% among Chinese adults. This prevalence is even higher, reaching 50%–70% in obese and diabetic individuals. A severe form of MASLD is metabolic dysfunction-associated steatohepatitis (MASH). These three diseases are intertwined, forming the core pathological chain of metabolic syndrome, jointly driving cardiovascular disease and all-cause mortality risk.

[0003] In the field of weight loss and blood sugar control, glucagon-like peptide-1 (GLP-1) receptor and multi-receptor agonists, represented by semaglutide and tirzepatide, have become the mainstream choice. These peptide drugs suppress appetite and delay gastric emptying by activating receptors such as GLP-1, but they have systemic drawbacks such as weight rebound after discontinuation, a high incidence of gastrointestinal adverse reactions (40%–50%), approximately 20%–30% of weight loss due to lean body mass loss, and the need for long-term subcutaneous injections.

[0004] There has long been a lack of effective drugs in the treatment of MASLD and MASH. Summary of the Invention

[0005] The inventors of this invention are the first to discover that anti-CD147 antibodies can play a role in the treatment and improvement of metabolic diseases, and for the first time expand the indications for CD147 antibodies to the field of metabolic diseases, adding a new target for the regulation of glucose and lipid metabolism. Based on the above findings, this invention seeks protection for the following technical solutions: The first technical solution provided by this invention is the application of a substance targeting CD147 in pharmaceutical manufacturing; wherein the drug is a drug for the prevention and / or treatment of metabolic-related diseases.

[0006] On the one hand, the metabolic-related diseases are diseases related to abnormal glucose metabolism, diseases related to abnormal lipid metabolism, obesity, cardiovascular metabolic diseases, and / or metabolic syndrome.

[0007] On the one hand, the metabolic-related diseases mentioned above are metabolic diseases caused by abnormal glucose and lipid metabolism.

[0008] Metabolic diseases characterized by abnormal glucose and lipid metabolism refer to metabolic diseases in which both glucose and lipid metabolism are abnormal.

[0009] On the one hand, the metabolic-related diseases mentioned are type 2 diabetes, prediabetes with impaired glucose tolerance, hyperlipidemia, hepatic steatosis, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), obesity, hypertension, coronary heart disease, cerebral infarction, peripheral vascular disease, myocardial infarction, heart failure, and / or metabolic syndrome formed by the intertwining of obesity, diabetes, and metabolic steatotic liver disease.

[0010] On the one hand, the metabolic-related diseases are caused by obesity and / or insulin resistance, or the metabolic-related diseases are caused by metabolic disorders resulting from obesity and / or insulin resistance. On the one hand, the metabolic-related diseases mentioned above are induced by a high-fat diet.

[0011] On the one hand, the drug prevents and / or treats the metabolic-related diseases by inhibiting food intake and / or improving excessive fat accumulation, and / or inhibiting hepatic steatosis, and / or improving insulin resistance; specifically, the drug inhibits food intake by inhibiting ghrelin levels; the improvement of excessive fat accumulation is to improve the excessive accumulation of subcutaneous and / or visceral fat.

[0012] Specifically, the ghrelin level refers to the content of ghrelin and / or the level at which ghrelin activation is inhibited.

[0013] On the one hand, the metabolic-related diseases mentioned can be diseases related to abnormal glucose metabolism. Diseases related to abnormal glucose metabolism include, but are not limited to, type 2 diabetes or glucose intolerance in prediabetes.

[0014] On the one hand, the metabolic-related diseases mentioned above may be lipid metabolism disorders. Lipid metabolism disorders include, but are not limited to, hyperlipidemia, hepatic steatosis, metabolic dysfunction-associated steatotic liver disease (MASLD), or metabolic dysfunction-associated steatohepatitis (MASH).

[0015] On the one hand, the metabolic-related disease mentioned is obesity.

[0016] On the one hand, the metabolic-related diseases mentioned are cardiovascular metabolic disorders. Cardiovascular metabolic disorders include, but are not limited to, hypertension, coronary heart disease, cerebral infarction, peripheral vascular disease, myocardial infarction, or heart failure.

[0017] On one hand, the aforementioned metabolic-related diseases are metabolic syndromes. Metabolic syndromes generally refer to diseases that simultaneously meet at least two of the following criteria: obesity, abnormal glucose metabolism, abnormal lipid metabolism, and cardiovascular metabolic disorders. Specifically, it can be a metabolic syndrome caused by abnormal glucose and lipid metabolism. More specifically, metabolic syndrome can be a metabolic syndrome formed by the interplay of obesity, diabetes, and metabolic fatty liver disease.

[0018] On the one hand, the metabolic-related diseases are caused by obesity and / or insulin resistance. Or more specifically, the metabolic-related diseases are caused by metabolic disorders resulting from obesity and / or insulin resistance.

[0019] As a specific embodiment, the metabolic-related disease is a disease caused by metabolic disorders resulting from obesity and / or insulin resistance; wherein the obesity and / or insulin resistance is induced by a high-fat diet.

[0020] On the one hand, the drug is a drug that reduces fat content and / or inhibits fat accumulation; On the one hand, the drug is a weight-reducing drug, specifically a drug that reduces weight by inhibiting food intake, and more specifically a drug that reduces weight by inhibiting ghrelin levels, thereby inhibiting food intake, and further reducing weight. On the one hand, the drug is a drug that inhibits weight gain and / or body fat accumulation in an organism; On the one hand, the drug is a drug that reduces the body fat percentage of an organism; On the one hand, the drug is a drug that increases the lean body mass percentage of an organism; On the one hand, the drug is a drug that reduces the body weight of an organism; On the one hand, the drug is a drug that reduces the amount of food ingested by an organism; On the one hand, the drug is a drug that reduces the amount of food an organism consumes, thereby reducing its weight; On the one hand, the drug is a drug that improves the body's resistance to insulin; that is, it enhances the patient's sensitivity to insulin.

[0021] On the one hand, the drug is a drug that reduces the subcutaneous fat content and visceral fat content of an organism; On the one hand, the drug is a drug that reduces lipid accumulation in the white adipose tissue of an organism; On the one hand, the drug is a drug that reduces the size of subcutaneous fat cells and visceral fat tissue cells in an organism; On the one hand, the drug is a drug that inhibits hepatic steatosis in organisms; On one hand, the drug is a drug that inhibits ghrelin in organisms, thereby suppressing food intake. More specifically, inhibiting ghrelin in organisms means reducing ghrelin levels and / or lowering activated ghrelin levels.

[0022] On the one hand, the drug in question is a weight-loss, blood sugar-lowering, and liver-protecting drug.

[0023] On the other hand, the drug may also be a drug that simultaneously has at least two of the above-mentioned pharmacological effects.

[0024] The aforementioned organisms refer to individuals suffering from any metabolic-related diseases.

[0025] The organism can also be any mammal other than a human.

[0026] On the one hand, the substance targeting CD147 can be an antibody against CD147, specifically an antibody against human CD147.

[0027] On the one hand, the anti-CD147 antibody is an F(ab')2 antibody against CD147.

[0028] The F(ab')2 antibody against CD147 is the remaining structure after removing the Fc region from the complete anti-CD147 IgG antibody, which is the F(ab')2 fragment of the complete anti-CD147 IgG antibody. Specifically, it includes the light chain variable region VL, the light chain constant region, the heavy chain variable region VH, CH1 in the heavy chain constant region, and the hinge region. A hinge region sequence is introduced at the C-terminus of CH1, so that the two heavy chains are linked through the hinge region disulfide bonds to form the F(ab')2 dimer structure.

[0029] The CDR1, CDR2, and CDR3 sequences in the variable regions of the antibody heavy chain and the antibody light chain of the F(ab')2 antibody can be any CDR sequence found in antibodies with anti-CD147 activity. As a specific embodiment, in the F(ab')2 antibody, the CDR1 sequence in the variable region of the antibody heavy chain is shown in SEQ ID NO:6, the CDR2 sequence in SEQ ID NO:7, and the CDR3 sequence in SEQ ID NO:8; the CDR1 sequence in the variable region of the antibody light chain is shown in SEQ ID NO:9, the CDR2 sequence in SEQ ID NO:9, and the CDR3 sequence in SEQ ID NO:10.

[0030] The CDR sequence can also be modified to optimize affinity or specificity through the following substitutions: A classic affinity maturation strategy combining random mutations in the CDR region with display screening can be employed. Random mutations can be introduced into the light and heavy chain CDR regions using error-prone PCR or DNA synthesis techniques to construct mutant libraries covering CDR1, CDR2, and CDR3. These libraries can then be displayed on the surface of bacteriophages or yeast cells, and multiple rounds of affinity screening can be performed targeting the recombinant CD147 extracellular domain protein to enrich high-affinity clones. Positive clones obtained through screening can be sequenced and subjected to SPR affinity verification to ultimately determine the affinity-optimized CDR sequence combination.

[0031] The frame region can be mouse-derived or further humanized, such as by replacing individual amino acids in the mouse FR with corresponding human amino acids to reduce immunogenicity. Another example is the use of CDR transplantation technology to transplant mouse CDRs into the fully human frame region to construct a fully human F(ab')2 antibody.

[0032] As a specific embodiment, the amino acid sequence of the light chain variable region is SEQ ID NO:1 or an amino acid sequence having more than 90% homology with SEQ ID NO:1, and the amino acid sequence of the heavy chain variable region is SEQ ID NO:2 or an amino acid sequence having more than 90% homology with SEQ ID NO:2.

[0033] Heavy chain constant region CH1: including but not limited to CH1 of IgG1 isotype, CH1 of IgG2 isotype, CH1 of IgG3 isotype, and CH1 of IgG4 isotype. Heavy chain constant region CH1 can be wholly human or partially human. As a specific example, the amino acid sequence of CH1 in the heavy chain constant region is SEQ ID NO:3.

[0034] Light chain constant region: including but not limited to the κ constant region and the λ constant region. As a specific example, the amino acid sequence of the light chain constant region is SEQ ID NO:4.

[0035] Hinge Region: The length of the hinge region in this invention can be shortened or lengthened to adjust the flexibility and stability of the F(ab')2 fragment. The hinge region sequence of this invention can adopt the hinge region sequence of IgG1, IgG2, or IgG4 to reduce the number of disulfide bonds and decrease the tendency for fragment aggregation. Cysteine ​​residues in the hinge region can also be mutated to serine or alanine to prevent the formation of unintended disulfide bonds. As a specific embodiment, the amino acid sequence of the hinge region is SEQ ID NO:5.

[0036] Any of the antibodies described above also fall within the scope of protection of this invention.

[0037] In addition to F(ab')2, the antibody fragments of the present invention can also take the following fragment forms: Fab fragment: a single light chain + a single heavy chain (containing VH-CH1), with a molecular weight of approximately 50 kDa, offering better permeability but with halved affinity; Bispecific F(ab')2: one arm targets CD147, and the other arm targets other metabolic regulatory molecules (such as GLP-1R and GIPR), achieving dual-target synergy.

[0038] The administration methods of the drug of the present invention include, but are not limited to, intravenous injection and oral administration.

[0039] This invention is the first to discover that anti-CD147 antibodies can play a role in the treatment and improvement of metabolic diseases, and for the first time expands the indications of CD147 antibodies to the field of metabolic diseases, adding a new target for the regulation of glucose and lipid metabolism.

[0040] This invention is the first to remove the Fc fragment from a complete anti-CD147 IgG antibody, forming a fragment antibody with a molecular weight of approximately 97 kDa. This fragment antibody has excellent effects on weight loss, lipid reduction, and insulin resistance reduction in patients with obesity and other metabolic diseases, and is expected to become an effective drug for treating metabolic-related diseases such as obesity, diabetes, metabolic-related fatty liver disease, or metabolic syndrome formed by the intertwining of obesity, diabetes, and fatty liver.

[0041] This invention also eliminates Fc-mediated metabolic side effects, i.e., avoids insulin resistance caused by competitive binding of the Fc segment to the insulin receptor; removes ADCC / CDC effector function, reducing the risk of immune activation in a chronic inflammatory environment; and enhances tissue permeability after molecular weight reduction, significantly improving distribution in adipose tissue and liver parenchyma. Attached Figure Description

[0042] Figure 1 The effects of G1601 on body weight and body fat percentage.

[0043] Figure 2 The effects of G1601 on energy intake and expenditure.

[0044] Figure 3 The effect of a single injection of G1601 on food intake and body weight.

[0045] Figure 4 The effects of G1601 on glucose tolerance and insulin tolerance.

[0046] Figure 5 The effect of G1601 on the weight of metabolism-related tissues.

[0047] Figure 6 The effects of G1601 on adipose tissue pathology.

[0048] Figure 7 The effects of G1601 on liver pathology.

[0049] Figure 8 The effect of G1601 on dietary hormones.

[0050] HFD+Vehicle is the antibody control; HFD indicates a high-fat diet, and Vehicle indicates the use of saline solution. Detailed Implementation

[0051] The following are some specific embodiments of the present invention. Unless otherwise specified, the technical means or reagents used are conventional methods and reagents known in the art.

[0052] The antibodies in the following examples are merely illustrative of the present invention. Any other anti-CD147 antibodies, as well as antibodies or antibody fragments modified based on anti-CD147 antibodies, or antibodies or antibody fragments modified in any way, are within the scope of protection of the present invention.

[0053] Example 1 Anti-CD147 F(ab')2 antibody and its preparation The internal code for the anti-CD147 F(ab')2 antibody in this embodiment is G1601. Specifically, it is the fragment remaining after removing the Fc region of the complete anti-CD147 IgG antibody, namely the F(ab')2 fragment.

[0054] The anti-CD147 F(ab')2 antibody of this embodiment is based on the murine VL and VH of CD147 antibody, combined with the human constant heavy chain 1 (CH1) (IgG1 CH1) and the κ light chain constant region, and was obtained by genetic engineering recombination and expression purification in CHO cells. Its complete protein has a molecular weight of approximately 97 kDa, 100% primary amino acid sequence coverage, and the N-terminal amino acid sequences of both the light and heavy chains are consistent with theoretical values. The amino acid sequences of VL and VH are shown in SEQ ID NO:1 and SEQ ID NO:2, respectively. The amino acid sequence of IgG CH1 is shown in SEQ ID NO:3, the amino acid sequence of the κ light chain constant region is shown in SEQ ID NO:4, and the amino acid sequence of the hinge region is shown in SEQ ID NO:5.

[0055] By using genetic engineering, a hinge region sequence was introduced at the C-terminus of the CH1 heavy chain, allowing the two heavy chains to be linked by disulfide bonds in the hinge region, forming an F(ab')2 dimer structure. This design preserves the complete antigen-binding function while removing the Fc segment, eliminating effector functions such as ADCC and CDC, and avoiding the Fc segment-mediated insulin receptor inhibition effect.

[0056] SEQ ID NO:1: Anti-CD147 F(ab')2 antibody light chain variable region (VL) amino acid sequence: PRT 107 SIVMTQTPTFLVVSAGDRVTITCKASQSVINDVAWYQQKPGQSPKLLIFY ASNRNTGVPDRFTGSGYGTDFTFTISTVQAEDLAVYFCQQDYSPPFTFGS GTKLEIK SEQ ID NO:2: Anti-CD147 F(ab')2 antibody heavy chain variable region (VH) amino acid sequence: PRT 117 EVKLEESGGGLVQPGGSMKLSCVASGFTFSDAWMDWVRQSPEKGLEW VAEIRSKANNHAPYYTESVKGRFTISRDDSKSIIYLQMNNLRAEDTGIYY CTRDSTATHWGQGTLVTVSA SEQ ID NO:3: Amino acid sequence of the heavy chain constant region (CH1) of the anti-CD147 F(ab')2 antibody: PRT 98 ASTKGPSVFPLAPSSKSGSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRV SEQ ID NO:4: Anti-CD147 F(ab')2 antibody light chain constant region (κ) amino acid sequence: PRT 107 RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSG NSQESVTEQDSKDSTYSLSSSTLTLSKADYEKHKVYACEVTHQGLSSPVTK SFNRGEC SEQ ID NO:5: Amino acid sequence of the hinge region of anti-CD147 F(ab')2 antibody: PRT 19 EPKSCDKTHTCPPCPAPEL The CDR1 sequence of the antibody heavy chain variable region is GFTFSDAW (SEQ ID NO:6), the CDR2 sequence is IRSKANNHAP (SEQ ID NO:7), and the CDR3 sequence is TRDSTATH (SEQ ID NO:8). The CDR1 sequence of the antibody light chain variable region is QSVIND (SEQ ID NO:9), the CDR2 sequence is YAS, and the CDR3 sequence is QQDYSPPFT (SEQ ID NO:10).

[0057] Example 2: Animal experiment on the treatment of obesity and metabolic disorders with G1601 2.1 Laboratory Animals and Grouping Six-week-old male humanized CD147 transgenic mice were fed a high-fat diet for 12 weeks to induce obesity and metabolic disorder models. They were then injected via tail vein with either 5 mg / kg G1601 monoclonal antibody or an equal volume of physiological saline, twice a week for 5 weeks.

[0058] 2.2 G1601 can significantly inhibit high-fat diet-induced weight gain and body fat accumulation. After grouping, mice were weighed at fixed times each week, and body fat percentage was measured using nuclear magnetic resonance imaging (NMR) at the experimental endpoint. Compared with the control group, the G1601 group showed significantly inhibited weight gain, significantly reduced body fat percentage, and significantly increased lean body mass percentage. Figure 1 ).

[0059] 2.3 G1601 reduces body weight by suppressing food intake. Metabolic cages were used to record food intake, oxygen consumption, and carbon dioxide production in two groups of mice to assess the effect of G1601 on energy intake and expenditure. When there was no difference in body weight, G1601 significantly reduced food intake in mice compared to the control group, while energy expenditure and other indicators were not the cause of body weight changes. Figure 2 ).

[0060] 2.4 A single injection of G1601 significantly suppressed food intake and reduced body weight. Metabolic cages were used to record changes in food intake and body weight in mice after a single injection of monoclonal antibody. Food intake decreased significantly within 5 days after the single antibody injection, with the most significant difference observed on day 4. Body weight showed a significant difference starting 72 hours after injection. Figure 3 ).

[0061] 2.5 G1601 effectively improves insulin tolerance In the glucose tolerance test, mice were fasted for 16 hours and then injected intraperitoneally with 1 g / kg glucose. Blood glucose levels were measured by tail vein sampling at 0, 30, 60, 90, and 120 minutes. An insulin tolerance test was performed at least one week later. Mice were fasted for 4 hours and then injected intraperitoneally with 0.5 IU / kg insulin. Blood glucose levels were measured by tail vein sampling at 0, 15, 30, 60, 90, and 120 minutes. G1601 did not improve glucose tolerance in obese mice, but it significantly improved insulin resistance. Figure 4 ).

[0062] 2.6 G1601 significantly reduced white adipose tissue and liver weight. Mice were sacrificed at the experimental endpoint, and metabolic-related tissues were isolated and weighed. G1601 significantly reduced subcutaneous adipose tissue and liver weight, and decreased visceral adipose tissue weight. Figure 5 ).

[0063] 2.7 G1601 significantly reduced lipid accumulation in white adipose tissue Adipose tissue was fixed, dehydrated, embedded, sectioned, and stained with hematoxylin and eosin (HE) to observe adipocyte size. G1601 significantly reduced the size of adipocytes in subcutaneous and visceral adipose tissue. Figure 6 ).

[0064] 2.8 G1601 significantly improved high-fat diet-induced hepatic steatosis. Liver tissue was embedded using OCT and frozen sections were prepared for HE and Oil Red staining to observe the degree of hepatic steatosis. G1601 significantly reduced lipid deposition in mouse liver ( Figure 7 ).

[0065] 2.9 G1601 inhibits food intake by reducing serum ghrelin levels. Blood was collected from the eyeballs, serum was separated, and serum ghrelin and activated ghrelin levels in mice were detected by ELISA. Compared with the control group, serum ghrelin and activated ghrelin levels in the G1601 group were significantly lower. Figure 8 ).

Claims

1. Application of substances targeting CD147 in pharmaceuticals; among which, The drug is a medication for the prevention and / or treatment of metabolic-related diseases.

2. The application according to claim 1, characterized in that: The metabolic-related diseases mentioned are diseases related to abnormal glucose metabolism, diseases related to abnormal lipid metabolism, obesity, cardiovascular metabolic diseases, and / or metabolic syndrome; Specifically, the metabolic-related diseases mentioned are metabolic diseases involving abnormal glucose and lipid metabolism; More specifically, the metabolic-related diseases include type 2 diabetes, prediabetes with impaired glucose tolerance, hyperlipidemia, hepatic steatosis, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), obesity, hypertension, coronary heart disease, cerebral infarction, peripheral vascular disease, myocardial infarction, heart failure, and / or metabolic syndrome formed by the interplay of obesity, diabetes, and metabolic fatty liver disease.

3. The application according to claim 1 or 2, characterized in that: The metabolic-related diseases are diseases caused by obesity and / or insulin resistance, or are diseases caused by metabolic disorders resulting from obesity and / or insulin resistance. More specifically, the metabolic-related diseases are induced by a high-fat diet.

4. The application according to any one of claims 1-3, characterized in that: The drug prevents and / or treats the metabolic-related diseases by inhibiting food intake and / or improving excessive fat accumulation, and / or inhibiting hepatic steatosis, and / or improving insulin resistance; specifically, the drug inhibits food intake by inhibiting ghrelin levels; the improvement of excessive fat accumulation refers to improving the excessive accumulation of subcutaneous and / or visceral fat.

5. The application according to any one of claims 1-4, characterized in that: The drug is a drug that reduces fat content and / or inhibits fat accumulation; And / or, the drug is a weight-reducing drug, specifically a drug that reduces weight by inhibiting food intake, and more specifically a drug that reduces weight by inhibiting ghrelin levels, thereby inhibiting food intake, and further reducing weight. And / or, the drug is a drug that improves an organism's resistance to insulin; And / or, the drug is a drug that inhibits weight gain and / or body fat accumulation in an organism; And / or, the drug is a drug that reduces the body fat percentage of an organism; And / or, the drug is a drug that increases the lean body mass percentage of an organism; And / or, the drug is a drug that reduces the body weight of an organism; And / or, the drug is a drug that reduces the amount of food ingested by an organism; And / or, the drug is a drug that reduces the amount of food an organism consumes, thereby reducing its body weight; And / or, the drug is a drug that reduces the subcutaneous fat content and / or visceral fat content of an organism; And / or, the drug is a drug that reduces lipid accumulation in the white adipose tissue of an organism; And / or, the drug is a drug that reduces the size of subcutaneous fat cells and visceral fat tissue cells in an organism; And / or, the drug is a drug that inhibits hepatic steatosis in organisms; And / or, the drug is a drug that inhibits ghrelin in an organism, thereby inhibiting food intake; And / or, the drug is a weight-loss, blood sugar-lowering, and liver-protecting drug; The organism in question is a patient with the aforementioned metabolic-related disease.

6. The application according to any one of claims 1-5, characterized in that: The substance targeting CD147 is an antibody against CD147, specifically an antibody against human CD147.

7. The application according to any one of claims 1-6, characterized in that: The anti-CD147 antibody is an F(ab')2 antibody against CD147.

8. The application according to any one of claims 1-7, characterized in that: In the F(ab')2 antibody, the CDR1 sequence of the antibody heavy chain variable region is shown in SEQ ID NO:6, the CDR2 sequence is shown in SEQ ID NO:7, and the CDR3 sequence is shown in SEQ ID NO:

8. The CDR1 sequence of the antibody light chain variable region is shown in SEQ ID NO:9, the CDR2 sequence is YAS, and the CDR3 sequence is shown in SEQ ID NO:

10.

9. The application according to any one of claims 1-8, characterized in that: The amino acid sequence of the light chain variable region is SEQ ID NO:1, and the amino acid sequence of the heavy chain variable region is SEQ ID NO:2; And / or, the amino acid sequence of CH1 in the heavy chain constant region is SEQ ID NO:3; the amino acid sequence of the light chain constant region is SEQ ID NO:4; and the amino acid sequence of the hinge region is SEQ ID NO:

5.

10. The antibody in any of the applications described in claims 1-9.

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