Immune drug for treating tumors and application

Abstract

The invention discloses an immune drug for treating tumors and application thereof, the immune drug comprises a viral vector, the viral vector expresses a protein with an amino acid sequence as shown in SEQ ID No.1, a nucleotide sequence for coding the SEQ ID No.1 is as shown in SEQ ID No.2, and the viral vector is a protein with an amino acid sequence as shown in SEQ ID No.1. An existing safe and effective virus tool is used as a carrier, and the nucleotide sequence is expressed in solid tumor cells and specifically recognized by an organism immune system to generate a hemolytic reaction similar to an autoimmune effect, so that the aim of killing the tumor cells is fulfilled.

Description

Technical Field

[0001] The present invention relates to the field of biomedical technology, and in particular to an immune drug for treating tumors and its application. Background Art

[0002] Tumors have become a major threat to human life and health, and their incidence rates are increasing year by year. Traditional tumor treatments include surgery, chemotherapy, and radiotherapy. Although they have certain therapeutic effects, the side effects are also very obvious. Emerging tumor treatment strategies such as targeted therapy and immunotherapy have brought hope to patients. In recent years, various forms of antibodies have been widely approved for cancer treatment, including monoclonal antibodies for targeted therapy or immune checkpoint inhibition, antibody-drug conjugates, and recombinant bispecific antibodies that target endogenous T cells to tumors. In addition, oncolytic virus therapy is an emerging tumor treatment method, and the first oncolytic virus was approved for marketing in 2015. Preclinical and clinical data show that the therapeutic activity of oncolytic viruses depends on the anti-tumor immune activation triggered by viral oncolysis. Therefore, immunotherapy combined with antibody therapy and oncolytic viruses has great potential for the treatment of solid tumors.

[0003] Oncolytic virus therapy uses oncolytic viruses to selectively infect and lyse tumor cells, allowing the virus to replicate and spread in the tumor. Oncolytic virus selectivity is based on intrinsic characteristics of tumor cells, such as unrestricted proliferation signals, increased nucleotide synthesis, defects in apoptosis pathways, and defects in antiviral defense mechanisms. The development of oncolytic viruses utilizes a variety of viruses with or without envelopes, DNA or RNA genomes, and a wide range of genome and particle sizes. Wild-type viruses, such as vesicular stomatitis virus, Newcastle disease virus, or parvovirus or vaccine strains (such as measles virus), are highly sensitive to the cellular antiviral defense of normal human cells, but will replicate and kill tumor cells that lack antiviral defense. Oncolytic viruses usually fuse ligands to binding glycoproteins on the cell surface, especially for enveloped viruses, oncolytic viruses have achieved free entry into tumor cells. The therapeutic activity of oncolytic viruses depends on oncolysis-induced, tumor-directed innate and adaptive immune responses. This oncolytic vaccination effect is caused by the release of tumor antigens and pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) during immunogenic cell lysis induced by oncolytic viruses. Studies have also shown that local oncolysis, after intratumoral injection of oncolytic viruses, can trigger systemic anti-tumor immunity in animals and patients, thereby mediating the destruction of metastatic lesions that the oncolytic viruses have not reached ("abscopal effect").

[0004] Most antibodies recognize tumor-associated antigens on tumor cells. Prominent examples are IgG molecules targeting CD20 for the treatment of B-cell malignancies, and antibodies targeting epidermal growth factor receptor or human epidermal growth factor receptor 2, which are approved for the treatment of different types of solid tumors, such as colorectal cancer, gastric cancer, lung cancer, and breast cancer. These antibodies exploit the natural functions of IgG molecules to destroy tumor cells by blocking the activity of target structures, inducing apoptosis, and / or through Fc-mediated effector functions (such as antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement). However, these activities are not always sufficient to effectively induce lasting tumor regression. Therefore, in second-generation development, the mode of action of antibodies has been expanded by using antibodies as targeting moieties to deliver cytotoxic compounds such as radionuclides, chemotherapeutic drugs, and toxins to tumor cells. An area where the use of therapeutic antibodies has rapidly expanded is the field of immuno-oncology, where antibodies are developed to initiate or promote anti-tumor immune responses. However, antibodies still face various obstacles to becoming effective and safe treatments. One of the main limitations of antibodies, especially for the treatment of solid tumors, is their often rather poor and heterogeneous tumor penetration after systemic application, which is a result of physical barriers and high interstitial fluid pressure limiting the extravasation and interstitial diffusion of large antibody molecules. In addition, the inherent biochemical properties of antibodies (such as surface charge) may affect the pharmacokinetic properties and their tissue distribution. Antibodies with high affinity preferentially accumulate around blood vessels, which is called the binding site barrier effect. Due to the lack of tumor-specific targets, the "hit the target, off the tumor" activity is further limited, which may lead to the side effects shown by bispecific T cell engagers and CAR-T therapies, which induce T cell reactivity against normal tissues.

[0005] In summary, both of the above-mentioned agents exhibit excellent tumor selectivity and pleiotropic effects, but also face challenges such as tumor heterogeneity and limited tumor penetration. An innovative strategy to address these challenges combines these two drug treatment strategies into a single, multitasking therapy. Autoimmune hemolytic anemia is believed to be anemia caused by increased red blood cell turnover due to an autoimmune mechanism. The immunopathogenesis is typically mediated by autoantibodies against red blood cell surface antigens, with the involvement of the mononuclear phagocyte system and T lymphocytes. Pathogenic autoantibodies target red blood cell membrane epitopes, providing a receptor-mediated extravascular hemolysis mechanism involving macrophages. Complement can interact with red blood cell-bound antibodies, promoting extravascular hemolysis or causing intravascular hemolysis through the formation of membrane attack complexes. Red blood cell antibodies can be alloantibodies or autoantibodies. They are typically of the IgG class (e.g., anti-D, warm autoantibodies) or IgM class (isoagglutinins: anti-A, anti-B, or cold autoantibodies). Inspired by the mechanism of autoimmune hemolytic anemia, treating tumor cells as red blood cells and allowing the body to produce a similar autoimmune hemolytic anemia against tumor cells, causing the tumor cells to lyse and die, can become a strategy for treating solid tumors.

[0006] The ABO blood group system is the most important blood group system in humans. Blood group incompatibility typically occurs when an A or B antigen is exposed to a person who has antibodies against those antigens. In the ABO blood group system, the DNA sequence of the "A" group-specific transferase was initially partially sequenced from human lung tissue. Subsequently, the various A, B, and O alleles were cloned and sequenced, and the sequence variations between them were identified. The fucosyltransferase expressed by the H gene (later identified as the FUT1 gene) is present in hematopoietic tissue and attaches fucose to the terminal galactose residue of the type 2 chain in an α1-2 linkage. This H antigen completes the receptor substrate and is required for the attachment of the final monosaccharide that distinguishes between the A and B antigens. In individuals with non-O blood groups, individuals with the A allele express an N-acetylgalactosaminyltransferase that attaches N-acetylgalactosamine to the terminal galactose residues of type 1 and type 2 chains in an α1-3 linkage, while individuals with the B allele express a galactosyltransferase allele that adds galactose to these residues in an α1-3 linkage. ABO blood group antibodies naturally occur in the human body and activate the body's immune system by recognizing blood group antigens, causing red blood cell lysis and death.

[0007] Therefore, those skilled in the art are committed to developing an immune drug for treating tumors and its application as well as the application of using the gene to treat tumor diseases. Summary of the Invention

[0008] In view of the above-mentioned defects of the prior art, the technical problem to be solved by the present invention is to provide an immune drug for treating tumors and its application, as well as the application of the gene for treating tumor diseases.

[0009] To achieve the above objectives, the present invention provides an immunotherapy drug for treating tumors, comprising a viral vector that expresses the amino acid sequence shown in SEQ ID No. 1. The amino acid sequence shown in SEQ ID No. 1 is as follows:

[0010] MWLRSHRQLCLAFLLVCVLSVIFFLHIHQDSFPHGLGLSILCPDRRLVTPPVAIFCLPGTAMGP

[0011] NASSSCPQHPASLSGTWTVYPNGRFGNQMGQYATLLALAQLNGRRAFILPAMHAALAPVFRITLPVLA

[0012] PEVDSRTPWRELQLHDWMSEEYADLRDPFLKLSGFPCSWTFFHHLREQIRREFTLHDHLREEAQSVLG

[0013] QLRLGRTGDRPRTFVGVHVRRGDYLQVMPQRWKGVVGDSAYLRQAMDWFRARHEAPVFVVTSNGMEWC

[0014] KENVDTPRAMRLLAMDRRLHRGKTLPCSHSATTPLPLAPSASGLPTWLAETLSTWPTSPCQTLSSRSL

[0015] SRRRPSCPSGWALMQTCLHSGHWLSLSSRRAEEVFHAVTWRRIPALWPRCCGRWPENQNATHFDLSFSC

[0016] LSWSCLVTGSAPEVCQEAWNNGGSAWLLGNLTICSASRCQGWSTPSQRCHRGRMSSWPLGWLPLSGRAR

[0017] STSTSSTSSSGSRTPPLGLCLPSRNTWLSSCSWRRRRSTSWWATVSTTMSSPTSWPRCPARWGPVGSC

[0018] QCWRWAPTSAGRTCPCAAWRSVTSASGASSARWITWCAWTWTWSSATMWAWRSLRCSAPCTPASTEAA

[0019] GRPSPTSAGPSPRPTSPRTRAISTTWGRSSGGRCKRCSGSPGPATRPWSTRPTASRPCGTTRATTSTY

[0020] CATNPPRCSPPSTCGTSSCWAGPPSGSGSLRCPRTTRRSGTR。

[0021] The nucleotide sequence encoding SEQ ID No.1 is shown as SEQ ID No.2, and the nucleotide sequence SEQ ID No.2 is as follows:

[0022] ATGTGGCTCCGGAGCCATCGTCAGCTCTGCCTGGCCTTCCTGCTAGTCTGTGTCCTCTCTGTAATCTT

[0023] CTTCCTCCATATCCATCAAGACAGCTTTCCACATGGCCTAGGCCTGTCGATCCTGTGTCCAGACCGCC

[0024] GCCTGGTGACACCCCCAGTGGCCATCTTCTGCCTGCCGGGTACTGCGATGGGCCCCAACGCCTCCTCT

[0025] TCCTGTCCCCAGCACCCTGCTTCCCTCTCCGGCACCTGGACTGTCTACCCCAATGGCCGGTTTGGTAA

[0026] TCAGATGGGACAGTATGCCACGCTGCTGGCTCTGGCCCAGCTCAACGGCCGCCGGGCCTTTATCCTGC

[0027] CTGCCATGCATGCCGCCCTGGCCCCGGTATTCCGCATCACCCTGCCCGTGCTGGCCCCAGAAGTGGAC

[0028] AGCCGCACGCCGTGGCGGGAGCTGCAGCTTCACGACTGGATGTCGGAGGAGTACGCGGACTTGAGAGA

[0029] TCCTTTCCTGAAGCTCTCTGGCTTCCCCTGCTCTTGGACTTTCTTCCACCATCTCCGGGAACAGATCC

[0030] GCAGAGAGTTCACCCTGCACGACCACCTTCGGGAAGAGGCGCAGAGTGTGCTGGGTCAGCTCCGCCTG

[0031] GGCCGCACAGGGGACCGCCCGCGCACCTTTGTCGGCGTCCACGTGCGCCGTGGGGACTATCTGCAGGT

[0032] TATGCCTCAGCGCTGGAAGGGTGTGGTGGGCGACAGCGCCTACCTCCGGCAGGCCATGGACTGGTTCC

[0033] GGGCACGGCACGAAGCCCCCGTTTTCGTGGTCACCAGCAACGGCATGGAGTGGTGTAAAGAAAACGTC

[0034] GACACTCCCAGGGCGATGTGACGTTTGCTGGCGATGGACAGGAGGCTACACCGTGGAAAGACTTTGCC

[0035] CTGCTCACACAGTGCAACCACACCATTATGACCATTGGCACCTTCGGCTTCTGGGCTGCCTACCTGGC

[0036] TGGCGGAGACACTGTCTACCTGGCCAACTTCACCCTGCCAGACTCTGAGTTCCTGAAGATCTTTAAGC

[0037] CGGAGGCGGCCTTCCTGCCCGAGTGGGTGGGCATTAATGCAGACTTGTCTCCACTCTGGACATTGGCT

[0038] AAGCCTCTCGAGGAGGGCAGAGGAAGTCTTCTAACATGCGGTGACGTGGAGGAGAATCCCGGCCCTAT

[0039] GGCCGAGGTGTTGCGGACGCTGGCCGGAAAACCAAAATGCCACGCACTTCGACCTATGATCCTTTTCC

[0040] TAATAATGCTTGTCTTGGTCTTGTTTGGTTACGGGGTCCTAAGCCCCAGAAGTCTAATGCCAGGAAGC

[0041] CTGGAACGGGGGTTCTGCATGGCTGTTAGGGAACCTGACCATCTGCAGCGCGTCTCGTTGCCAAGGAT

[0042] GGTCTACCCCCAGCCAAAGGTGCTGACACCGTGGAAGGATGTCCTCGTGGTGACCCCTTGGCTGGCTC

[0043] CCATTGTCTGGGAGGGCACGTTCAACATCGACATCCTCAACGAGCAGTTCAGGCTCCAGAACACCACC

[0044] ATTGGGTTAACTGTGTTTGCCATCAAGAAATACGTGGCTTTCCTGAAGCTGTTCCTGGAGACGGCGGA

[0045] GAAGCACTTCATGGTGGGCCACCGTGTCCACTACTATGTCTTCACCGACCAGCTGGCCGCGGTGCCCC

[0046] GCGTGACGCTGGGGACCGGTCGGCAGCTGTCAGTGCTGGAGGTGGGCGCCTACAAGCGCTGGCAGGAC

[0047] GTGTCCATGCGCCGCATGGAGATGATCAGTGACTTCTGCGAGCGGCGCTTCCTCAGCGAGGTGGATTA

[0048] CCTGGTGTGCGTGGACGTGGACATGGAGTTCCGCGACCATGTGGGCGTGGAGATCCTGACTCCGCTGT

[0049] TCGGCACCCTGCACCCCAGCTTCTACGGAAGCAGCCGGGAGGCCTTCACCTACGAGCGCCGGCCCCAG

[0050] TCCCAGGCCTACATCCCCAAGGACGAGGGCGATTTCTACTACATGGGGGCGTTCTTCGGGGGGTCGGT

[0051] GCAAGAGGTGCAGCGGCTCACCAGGGCCTGCCACCAGGCCATGATGGTCGACCAGGCCAACGGCATCG

[0052] AGGCCGTGTGGCACGACGAGAGCCACCTGAACAAGTACCTACTGCGCCACAAAACCCACCAAGGTGCTC

[0053] TCCCCCGAGTACTTGTGGGACCAGCAGCTGCTGGGCTGGCCCGCCGTCCTGAGGAAGCTGAGGTTCACTGCGGTGCCCAAGAACCACCAGGCGGTCCGGAACCCGTGA.

[0054] Furthermore, the viral expression vector is an oncolytic virus, which specifically expresses B blood type antigen on the surface of tumor cells.

[0055] Furthermore, the viral expression vector includes any one of an adenoviral vector, a lentiviral vector, an adeno-associated viral vector or a measles viral vector, or a combination of at least two of them.

[0056] Furthermore, the immune drug also includes pharmaceutically acceptable excipients.

[0057] Furthermore, the excipients include any one or a combination of at least two of carriers, cytokines, diluents, excipients, fillers, adhesives, wetting agents, disintegrants, emulsifiers, solubilizers, osmotic pressure regulators, surfactants, coating materials, colorants, pH regulators, immune factors, antioxidants, antibacterial agents or buffers.

[0058] Furthermore, the administration route of the immune drug includes any one of interventional therapy introduction, intratumor injection, intravenous injection, intraperitoneal injection, intramuscular injection or subcutaneous injection, or a combination of at least two thereof.

[0059] Furthermore, the administration route of the immune drug is intratumoral injection, and the administration route is to select one point in each of the five directions of the tumor: east, south, west, and middle.

[0060] The present invention also provides a method for preparing the above-mentioned immune drug for treating tumors, comprising the following steps:

[0061] (1) constructing the nucleotide sequence as shown in SEQ ID No. 2 into a viral expression vector, wherein the viral expression vector comprises any one or a combination of at least two of pspax2, pMD2G or pLVX-IRES-ZsGreen1;

[0062] (2) The viral expression vector obtained in step (1) is transferred into 293T cells, and pharmaceutically acceptable excipients are added to obtain the immune drug.

[0063] The present invention also provides a use of the above-mentioned immune drug in constructing immune cell or mouse tumor models.

[0064] The beneficial effects of the present invention are as follows: the immunotherapy drug for treating tumors of the present invention and the amino acid sequence contained in the application, by using the currently safe and effective viral tools as carriers, expresses the sequence in tumor cells and is specifically recognized by the body's immune system to produce a hemolytic reaction similar to an autoimmune effect, thereby achieving the purpose of eliminating tumor cells.

[0065] ABO blood type antibodies naturally exist in the human body. By recognizing blood type antigens, they cause red blood cell lysis and death, thereby activating the human immune system. Blood type antigens bind to corresponding antibodies in human serum, stimulating the human immune system, inducing red blood cell lysis, eliminating tumor cells, and reducing tumor size. Patients with type A blood choose to receive treatment with type B blood antigens, while patients with type B blood choose to receive treatment with type A blood antigens. This activates the human immune system to produce and lyse tumor cells, thereby achieving the goal of eliminating the tumor. By applying the immune effects of blood type antibodies to tumor treatment, the destruction of tumor cells can be achieved by a mechanism similar to the destruction of red blood cells following blood type incompatibility. This may become a new method for treating tumors and preventing tumor drug resistance.

[0066] The immune drug provided in the present invention uses a lentiviral vector as a tool and ABO blood type antigens as tumor expression proteins, changing the traditional systemic medication method and adopting a local injection method for solid tumors. It improves the treatment effect of tumors while reducing side effects in tumor patients, and at the same time can prevent tumor cells from developing drug resistance, thereby prolonging the life of tumor patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0067] Figure 1 It is an observation chart of the efficacy of lentiviral therapy and immune drugs used to treat tumors;

[0068] Figure 2 It is a graph of tumor growth after carrying immune drugs for tumor treatment and using lentivirus therapy;

[0069] Figure 3 This is a comparison chart of tumor volume changes after treatment with immune drugs and lentivirus;

[0070] Figure 4 This is a comparison chart showing the degree of tumor volume reduction after treatment with immune drugs and lentivirus;

[0071] Figure 5 This is a comparison chart of the changes in tumor weight after treatment with immune drugs for tumor treatment and lentivirus therapy;

[0072] Figure 6 This is an observation chart of the degree of tumor weight reduction after carrying immune drugs for treating tumors and applying lentivirus treatment. DETAILED DESCRIPTION

[0073] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0074] All features disclosed in this specification, or all steps in the disclosed methods or processes, except mutually exclusive features and / or steps, may be combined in any manner and, unless otherwise stated, may be replaced by other equivalent or alternative features with similar purposes, that is, unless otherwise stated, each feature is merely one embodiment of a series of equivalent or similar features.

[0075] In the following examples, unless otherwise specified, the reagents, consumables, and instruments used can be purchased from conventional manufacturers; the experimental methods used are conventional experimental methods in the art.

[0076] In the preparation method, whether synthesizing the nucleotide sequence, connecting the fragment into the vector, or using packaging cells for packaging, all can be obtained by using experimental methods well known to those skilled in the art.

[0077] The relevant information of reagents, consumables and instruments used in the following examples is as follows:

[0078] Mice: Female Babl / c mice aged 6 to 8 weeks (purchased from Beijing Huafukang Company) were immunized once a week after the first immunization with B blood group antigen; they were housed under SPF conditions for three consecutive weeks in cages with a maximum of five mice per cage at the Experimental Animal Center of Southern Medical University.

[0079] Type B red blood cell suspension: from Shanghai Blood Biopharmaceutical Co., Ltd. (China), 10 ml / tube.

[0080] CT26 cells were obtained from the Cell Resource Center of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. They were cultured at 37°C in a humidified atmosphere of 5% CO2 in RPMI-1640 medium (Thermo Fisher, USA) supplemented with 10% fetal bovine serum. 2.5 × 10 6 / ml, 200μl.

[0081] Lentivirus-B antigen: donated by Beijing Li Keli Laboratory, 5×10 7 / ml, 200μl.

[0082] Example 1: This example provides an immune drug for treating tumors and a preparation method thereof, comprising the following steps:

[0083] (1) The nucleotide sequence shown in SEQ ID No. 2 was constructed into a viral expression vector, wherein the viral expression vector was pLVX-IRES-ZsGreen1 (donated by Beijing Li Keli Laboratory);

[0084] (2) The viral expression vector obtained in step (1) is transferred into 293T cells, the therapeutic virus is packaged in the 293T cells, and pharmaceutically acceptable excipients are added to obtain the immune drug.

[0085] Example 2: Observe the therapeutic effect of mouse tumors through mouse experiments. The specific operation steps are as follows:

[0086] (1) Female Babl / c mice aged 6 to 8 weeks were housed under SPF conditions for three consecutive weeks. A 5% red blood cell suspension (100 μL) of type B red blood cell suspension from Shanghai Blood Biopharmaceutical Co., Ltd. (China) was diluted and intraperitoneally injected into the mice once a week to construct a mouse model capable of producing type B blood antibodies.

[0087] (2) Seven days after the last immunization, 5×10 CT26 cells were inoculated into the armpit of the mice. 5 / mouse.

[0088] (3) Five days later, lentivirus-B antigen (1×10 7 / mouse, 200 μl) was the experimental group, and the control group was the empty virus group.

[0089] (4) Drug injections were performed on the first, third, and seventh days after treatment. To prevent viral drugs from entering the blood circulation, the injections were performed in small amounts at the edge of the tumor and in more selected locations. The selected locations were selected at one point each in the east, south, west, north, and center directions of the tumor.

[0090] (5) When the tumor volume reaches 1000 mm 3When the maximum tumor diameter reached 15 mm or the tumor ulcerated, the mice were immediately killed by cervical dislocation. After killing the mice, the tumor tissue was removed from the axilla and weighed. The average tumor weight and standard deviation of each group of mice were calculated. At this time, the tumor volume of the mice was measured and recorded. The formula for calculating tumor volume is V = length × width 2 ×0.50.

[0091] The percentage of tumor volume reduction = (tumor volume of each mouse - average volume of the control group) / average volume of the control group.

[0092] Percentage reduction of tumor weight = (tumor weight per mouse - average weight of control group) / average weight of control group.

[0093] like Figures 1 to 6 The experimental results shown in Figure 2 are as follows, where Con is the control group and B antigen is the experimental group, i.e., the B antigen group. Figure 1 As shown in Figure 3, the tumor size in the experimental group was significantly larger than that in the control group. Figure 2 As shown in Figure 3, the tumor growth rate in the experimental group was significantly slower than that in the control group. Figure 3 As shown in Figure 3, the tumor volume of the experimental group was significantly smaller than that of the control group. Figure 4 As shown in Figure 2, the percentage of tumor volume reduction in the experimental group was significantly greater than that in the control group. Figure 5 As shown in Figure 3, the tumor weight of the experimental group was significantly smaller than that of the control group. Figure 6 As shown in the figure, the percentage of tumor weight reduction in the experimental group was significantly greater than that in the control group.

[0094] In summary, the immune drug provided by the present invention can not only shrink tumors, but also has a simple treatment method. It changes the traditional systemic medication method and adopts the local injection method of solid tumors. It improves the treatment effect of tumors while reducing side effects in tumor patients and can also prevent tumor cells from developing drug resistance.

[0095] The present invention provides the preferred embodiments described above in detail. It should be understood that those skilled in the art can make numerous modifications and variations based on the concepts of the present invention without inventive effort. Therefore, any technical solution that can be derived by those skilled in the art through logical analysis, reasoning, or limited experimentation based on the concepts of the present invention and the prior art should be within the scope of protection defined by the claims.

Claims

1. An immune drug for treating tumors, characterized by: The invention comprises a viral vector which expresses a protein having an amino acid sequence as shown in SEQ ID No.

1.

2. The immunotherapy drug for treating tumors according to claim 1, characterized in that: The nucleotide sequence encoding SEQ ID No. 1 is shown in SEQ ID No.

2.

3. The immunotherapy drug for treating tumors according to claim 1, wherein: The viral expression vector is an oncolytic virus, which specifically expresses B blood type antigen on the surface of tumor cells.

4. The immunotherapy drug for treating tumors according to claim 1, wherein: The viral expression vector includes any one of an adenoviral vector, a lentiviral vector, an adeno-associated viral vector or a measles viral vector, or a combination of at least two of the vectors.

5. The immunotherapy drug for treating tumors according to claim 1, wherein: The immune drug also includes pharmaceutically acceptable excipients.

6. The immunotherapy drug for treating tumors according to claim 5, characterized in that: The excipients include any one or a combination of at least two of carriers, cytokines, diluents, excipients, fillers, adhesives, wetting agents, disintegrants, emulsifiers, cosolvents, solubilizers, osmotic pressure regulators, surfactants, coating materials, colorants, pH regulators, immune factors, antioxidants, antibacterial agents or buffers.

7. The immunotherapy drug for treating tumors according to claim 1, characterized in that: The administration route of the immune drug includes any one of interventional therapy introduction, intratumoral injection, intravenous injection, intraperitoneal injection, intramuscular injection or subcutaneous injection, or a combination of at least two thereof.

8. The immunotherapy drug for treating tumors according to claim 7, characterized in that: The administration route of the immune drug is intratumoral injection, and the administration route is to select one point in each of the five directions of the tumor: east, south, west, and middle.

9. Use of the immune drug according to claim 1 in constructing immune cell or mouse tumor models.

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