34 results about "Clear cell carcinoma" patented technology

The invention provides a preparation method and application of a CD70 specific nano antibody molecular imaging probe. The probe comprises a tumor targeting group, radionuclide and a bifunctional chelating agent, the tumor targeting group is a CD70 specific nano antibody; the CD70 specific nano antibody is R8B4, and the amino acid sequence of the R8B4 is as shown in SEQ ID No. 1. The probe provided by the invention can realize noninvasive diagnosis of solid tumors such as renal clear cell carcinoma and malignant tumors of a blood system; reabsorption of the compound in the kidney is effectively inhibited through charge adjustment, kidney uptake is remarkably reduced, non-specific signals are reduced, the signal-to-noise ratio during targeted imaging or treatment is increased, and the imaging quality and treatment safety are improved. The probe not only has a wide application prospect in tumor diagnosis, but also provides a new technical support for targeted therapy and individualized precision medical treatment, and has important scientific research and clinical application values.

The invention relates to the technical field of microorganisms, and particularly discloses a product for predicting tumor cell occurrence and metastasis risks and treating tumors by using a microbial marker. The cancers related to the invention comprise colon adenocarcinoma, head and neck squamous cell carcinoma, renal clear cell carcinoma, renal papillary cell carcinoma, hepatocellular carcinoma, lung squamous cell carcinoma, prostate adenocarcinoma, gastric adenocarcinoma, thyroid carcinoma, breast invasive carcinoma, uveal melanoma, esophageal carcinoma and the like. As a marker for predicting the occurrence and metastasis risk of tumor cells. The invention also screens specific microorganisms of healthy tissues relative to tumor tissues as potential means for treating tumors. The screened flora marker is high in sensitivity and good in specificity, and a new method is provided for tumor cell generation and metastasis monitoring and tumor treatment.

The present invention provides an RNA-based tumor vaccine, a preparation method, an immune adjuvant, a vector and an application. The tumor vaccine can specifically act on tumors with positive expression of GPC3, such as hepatocellular carcinoma, ovarian clear cell carcinoma, yolk sac carcinoma, etc. The tumor vaccine includes circular RNA capable of encoding an immunogenic polypeptide. The circular RNA is configured to be capable of specifically encoding the immunogenic polypeptide GPC3. The circ-GPC3 in the present invention has a covalently closed-loop structure that can protect it from exonuclease-mediated degradation, has a longer half-life and higher stability compared to mRNA, and can ensure the continuous expression of immunogenic proteins. By artificially modifying and introducing a ribosome entry site (IRES) modification, the present invention can increase the translation efficiency of tumor-specific antigen RNA.

The application provides a polymer carbon nitride@Hittorf red phosphorus heterostructure and application thereof in preparation of a medicine for targeted treatment of renal clear cell carcinoma, and belongs to the technical field of nano medicines. The application designs a near-infrared light response Hittorf red phosphorus (HP) modified polymer carbon nitride heterostructure (PCN@HP) based on a simple chemical vapor deposition (CVD) method. Experimental research finds that the HP nanorods vertically grown on the PCN exhibit wide and strong light absorption in the near-infrared range. In-vivo and in-vitro experiments prove that under near-infrared light irradiation, when the concentration of the suspension is 100 μg / mL, the tumor inhibition rate reaches 100%. Notably, the composite has no damage to normal tissues and cells, but it has obvious targeted inhibition effect on deep ccRCC cells in the body. In addition, the composite material has good biocompatibility and spontaneous light effect, and can be completely metabolized in the body within 48 hours, and is a kind of nanoparticle with imaging and PDT / PTT synergistic treatment, and can be used for efficient tumor nano treatment.

The invention provides a renal clear cell carcinoma pazopanib drug-resistant cell strain as well as a construction method and application thereof, the preservation number of the renal clear cell carcinoma drug-resistant cell strain is GDMCC NO: 65811, and the renal clear cell carcinoma drug-resistant cell strain is a pazopanib drug-resistant cell strain of 786-O. The Pazopanib is constructed in a manner of inducing the proliferation of kidney cancer cells 786-O in the Pazopanib by adopting a method of gradually increasing the concentration, and the drug resistance molecular mechanism of the Pazopanib is analyzed and read comprehensively through transcriptome, so that a new treatment idea is provided for clinically coping with the drug resistance of the Pazopanib.

The invention discloses an intermediate silk protein as a biomarker for predicting the staging, prognosis and drug resistance of renal clear cell carcinoma and application of the intermediate silk protein. By detecting the IFFO1 expression level of a ccRCC patient tissue specimen and analyzing a database, a new insight is provided for taking the expression quantity of the IFFO1 as a ccRCC biomarker. By changing the expression level of IFFO1 in the cell, the increase in proliferation, transfer and clone generation of the ccRCC cell as well as the improvement in genome stability are detected. In addition, after the IFFO1 is expressed in the ccRCC cells, the tolerance degree to sunitinib is increased, and the expression quantity of the IFFO protein family in the constructed ccRCC drug-resistant cells is increased. Researches show that the IFFO protein in ccRCC stabilizes a genome and promotes the tolerance of cells to a DNA damage inducer and a tyrosine kinase inhibitor sunitinib, molecular mechanism research and drug development taking IFFO as a target spot are beneficial to improvement of a treatment effect, and the IFFO protein has clear and beneficial practical application value.

The present invention provides a CD70-specific nanoantibody, a molecular imaging probe, and a preparation method and application thereof. The probe includes a tumor-targeting group, a radionuclide, and a bifunctional chelator; the tumor-targeting group is a CD70-specific nanoantibody; the CD70-specific nanoantibody is RD06, and the amino acid sequence of RD06 is shown in SEQ ID No. 1. The probe of the present invention can achieve non-invasive diagnosis of solid tumors such as renal clear cell carcinoma and hematological malignancies; and through charge adjustment, it effectively inhibits its reabsorption in the kidney, significantly reduces renal uptake, reduces nonspecific signals, improves the signal-to-noise ratio during targeted imaging or treatment, and improves imaging quality and treatment safety. This probe not only has broad application prospects in tumor diagnosis, but also provides new technical support for targeted therapy and personalized precision medicine, and has important scientific research and clinical application value.

This invention discloses the application of urinary microvesicle proteins as diagnostic markers for renal cell carcinoma. The protein markers derived from urinary extracellular vesicles associated with clear cell renal carcinoma are characterized by being selected from one or more of the following proteins: CSPG4, AQP1, PLIN2, CA9, and HAVCR1. The invention also describes the application of reagents for detecting these protein markers in the preparation of auxiliary diagnostic reagents for clear cell renal carcinoma. The inventors, using flow cytometry, analyzed 200 patients and found that five proteins derived from urinary extracellular vesicles could effectively distinguish patients with clear cell renal carcinoma from controls (including healthy individuals, patients with benign renal tumors, patients with benign renal cysts, and patients with chronic kidney disease).

The present invention relates to the use of GMFB protein as a biological marker for renal clear cell carcinoma. The present invention analyzed the expression level of GMFB in the KIRC patient population in the TCGA database and clarified that GMFB is associated with the pathogenesis of KIRC. Next, the prognosis of KIRC patients with different GMFB expression levels was analyzed, and it was found that the expression level of GMFB was significantly correlated with the prognosis of KIRC patients. Finally, CCK8 experiments confirmed that knocking down GMFB can significantly increase the viability of renal clear cell carcinoma cells, while overexpressing GMFB can significantly inhibit the viability, proliferation, migration and invasion ability of renal clear cell carcinoma cells, and significantly inhibit the mitochondrial membrane potential of renal clear cell carcinoma cells. The present invention provides a new therapeutic target for renal clear cell carcinoma.

The application discloses a traditional Chinese medicine composition for treating renal clear cell carcinoma and a preparation method and application thereof, and belongs to the technical field of medicines. The traditional Chinese medicine composition provided by the application comprises ginseng, astragalus, atractylodes, poria cocos, herba impatiens, oldenlandia, zedoary, dogwood fruit, ligustrum lucidum and prunella vulgaris. The traditional Chinese medicine composition provided by the application is scientific and reasonable in combination, can support healthy qi and eliminate pathogenic factors, clear heat and resolve toxins, activate blood and resolve stasis, and soften and resolve hard masses. The clinical experimental results show that the traditional Chinese medicine composition provided by the application can effectively treat renal clear cell carcinoma, and the treatment efficiency is better than that of the targeted drug sorafenib; and the medicine is safe, has no obvious toxic and side effects, and performs well in improving patient's traditional Chinese medicine syndromes, improving the quality of life and reducing the level of tumor markers. The application provides a new idea and method for treating renal clear cell carcinoma, and has significant clinical significance and important popularization value.

The invention discloses an auxiliary method for prognosis prediction of renal clear cell carcinoma, which comprises the following steps of: extracting four encoders by multi-modal representation and acquiring multi-modal knowledge; extracting three types of knowledge components from the CT image and the pathological image: individual knowledge only existing in a single mode, common knowledge existing among multiple modes and derivative knowledge obtained through interaction among the modes; optimal weights are dynamically allocated to different types of knowledge through a self-adaptive fusion strategy, so that optimal fusion features are obtained; and the extreme learning machine is used to predict each center feature so as to obtain a prediction result of the ccRCC patient. In the training process, through the guiding loss of the knowledge level and the sample level, different knowledge is more discriminative and distinctive. The ccRCC prognosis evaluation performance is effectively improved, so that the auxiliary diagnosis effect is achieved.

The present invention provides a pazopanib-resistant renal clear cell carcinoma cell line, a construction method, and an application thereof. The deposit number of the renal clear cell carcinoma cell line is GDMCC NO: 65811. The renal clear cell carcinoma cell line is a 786-O pazopanib-resistant cell line. The cell line is constructed by inducing the proliferation of renal cancer cells 786-O in the presence of pazopanib by gradually increasing the concentration of pazopanib. Through comprehensive transcriptome analysis, the molecular mechanism of drug resistance is interpreted, providing a new treatment strategy for clinical treatment of drug resistance.

The invention provides a renal clear cell carcinoma patient prognosis and drug therapy sensitivity evaluation model, which can accurately predict clinical prognosis conditions of renal clear cell carcinoma and sensitivity to various drug treatments, realizes layering of relapse / metastasis risks of patients and accurate prediction of targeting / immunotherapy drug sensitivity, and has a good application prospect. The method has clinical potential in the aspect of guiding treatment decisions to obtain better treatment results.

Heterocyclic compounds, their stereoisomers and their pharmaceutically acceptable salts are useful in the treatment of many types of cancers, such as cancers of the breast, prostate, pancreatic, gastric, lung, colon, rectum, esophagus cancer, duodenum, tongue, pharynx, liver, kidney, bile duct, uterine body, cervix, ovaries, urinary bladder, and skin. Other cancers to be treated include brain tumor, neurinoma, clear cell carcinoma, non-small cell lung cancer, small cell lung cancer, hemangioma, malignant lymphoma, malignant melanoma, thyroid cancer, bone tumor, vascular fibroma, glioblastoma, Neuroblastoma, sarcoma, neuroendocrine tumors, retinoblastoma, penile cancer, pediatric solid cancer, renal cell carcinoma, lymphoma, myeloma, leukemia, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia (CEL), chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), hairy cell leukemia, cutaneous T-cell lymphoma (CTCL), multiple myeloma (MM), myeloproliferative neoplasms (MPN), Myelodysplastic syndrome (MDS), polycythemia vera (PV), essential thrombocythemia, essential thrombocytosis (ET), and myelofibrosis (MF), and also including their metastases.

The present invention provides a shRNA for targeted silencing of RhoJ, its use, a recombinant plasmid and a lentiviral vector, which relate to the field of biomedical technologies. The nucleotide sequence of the sense strand of the shRNA for targeted silencing of RhoJ is as shown in SEQ ID No.1 or SEQ ID No.3, and the nucleotide sequence of the antisense strand of the shRNA is as shown in SEQ ID No.2 or SEQ ID No.4. The shRNA for targeted silencing of RhoJ of the present invention can significantly reduce the expression of RhoJ in renal clear cell carcinoma A498 cells, and inhibit the proliferation, invasion and migration of renal clear cell carcinoma A498 cells.

The invention discloses an automatic grading and classifying method for progressive kidney cancer based on a non-DCCD subtype marker, which comprises the following steps: taking an ACSM2A gene, a GATM gene and an LRP2 gene as marker genes for expressing renal clear cell carcinoma tissue samples, and performing DAB color development, nuclear staining, dehydration mounting and image scanning operation on each renal clear cell carcinoma tissue sample to obtain an immunohistochemical staining image; obtaining the staining intensity score of the immunohistochemical staining image of each marker gene antibody corresponding to each renal clear cell carcinoma tissue sample, and identifying the renal clear cell carcinoma tissue sample; performing image segmentation and cell counting on the immunohistochemical staining image to obtain a positive cell proportion score corresponding to each renal clear cell carcinoma tissue sample; classifying the renal clear cell carcinoma tissue sample as a progressive renal clear cell carcinoma patient or a non-progressive renal clear cell carcinoma based on the non-DCCD score; according to the invention, rapid and accurate screening of progressive renal clear cell carcinoma patients is realized, the realization mode is simple, and the cost is low.

The invention provides application of an MASP1 marker in preparation of a product for diagnosing and evaluating prognosis condition of renal clear cell carcinoma, and belongs to the technical field of renal clear cell carcinoma markers. Researches find that MASP1 expression in renal clear cell carcinoma tissues is significantly reduced, and the MASP1 expression level has significant correlation with good clinical prognosis of renal clear cell carcinoma patients. After MASP1 expression is inhibited, the level of branched chain amino acid in renal clear cell carcinoma cells is remarkably increased, key enzymes of related pathways are changed, end products of the renal clear cell carcinoma cells are accumulated, and metabolites generated after MASP1 inhibition have remarkable correlation with poor clinical prognosis of renal clear cell carcinoma patients. The MASP1 is used as a marker for diagnosing and evaluating the prognosis condition of the patient with the clear cell carcinoma of kidney, and has high sensitivity and specificity.

The present application relates to the field of cancer diagnosis, and particularly relates to a gene combination for prognosis evaluation of renal clear cell carcinoma and application of the gene combination in preparation of a kit for prognosis evaluation of renal clear cell carcinoma. The gene combination of the present application is derived from a molecular marker significantly related to cancer embolus of renal clear cell carcinoma. Discovery of the gene combination model provides a brand-new strategy for predicting recurrence risk and long-term survival condition of patients after surgery of renal clear cell carcinoma. The gene combination plays an important role in judging prognosis of patients with renal clear cell carcinoma, can evaluate risk level of tumor progression or death of patients after surgery of renal clear cell carcinoma, helps clinicians to implement individualized precision treatment strategy, improves survival rate of patients after surgery, and has important guiding significance for follow-up monitoring and sequential treatment management of patients after surgery of renal clear cell carcinoma.

The invention discloses a traditional Chinese medicine composition for treating renal clear cell carcinoma as well as a preparation method and application thereof, and belongs to the technical field of medicines. The traditional Chinese medicine composition provided by the invention comprises ginseng, astragalus membranaceus, bighead atractylodes rhizome, poria cocos, sculellaria barbata, oldenlandia diffusa, curcuma zedoary, dogwood, glossy privet fruit and selfheal. The traditional Chinese medicine composition provided by the invention is scientific and reasonable in compatibility, and can strengthen body resistance to eliminate pathogenic factors, clear away heat and toxic materials, promote blood circulation to remove blood stasis and soften hardness to dissipate stagnation. Clinical experiment results show that the traditional Chinese medicine composition provided by the invention can be used for effectively treating the renal clear cell carcinoma, and the treatment effective rate is superior to that of targeted medicine sorafenib; the traditional Chinese medicine composition is safe to take, has no obvious toxic or side effect, and has excellent performance in the aspects of improving traditional Chinese medicine syndromes of patients, improving life quality and reducing tumor marker level. The invention provides a new thought and method for treating the clear cell renal carcinoma, and has remarkable clinical significance and important popularization value.

The invention belongs to the technical field of biological medicine, and discloses a method for analyzing an action target of artemisinin for treating renal clear cell carcinoma based on network pharmacology and a molecular docking technology, and the method comprises the following steps: S1, screening the action target of an artemisinin active component; s2, identifying candidate disease targets; s3, acquiring an intersection target point; s4, constructing a protein-protein interaction network and performing network topology analysis; s5, core target biological function and molecular action signal path analysis and visualization; s6, constructing an artemisinin-renal clear cell carcinoma-target spot-pathway network diagram; s7, exploring an action mechanism of artemisinin for improving the renal clear cell carcinoma based on a molecular docking technology; s8, carrying out survival analysis on the core target spot based on the TCGA database, and drawing a Kaplan-Meier curve; and S9, observing the influence of artemisinin and derivatives thereof on the activity of renal clear cell carcinoma 786-O cells by adopting a CCK-8 method. Network pharmacology and molecular docking technologies are applied, multiple omics data are integrated from the perspective of system biology, a drug-target-disease network is constructed, the interaction between artemisinin and renal clear cell carcinoma related targets is deeply analyzed, and the action mechanism of artemisinin on the aspects of genes, proteins, signal channels and the like is comprehensively revealed.

The present invention discloses a liquid biopsy marker and a therapeutic target for clear cell renal cell carcinoma and their applications, belonging to the field of clinical diagnosis and treatment. Through bioinformatics analysis, it is found that the mRNA of PD-L2 in clear cell renal cell carcinoma is highly expressed after carcinogenesis, and is higher than the expression level of the mRNA of PD-L1, and is also related to poor staging. Further immunohistochemistry is used to verify the expression and localization of PD-L2 in clear cell renal cell carcinoma and adjacent tissues, and it is found that PD-L2 is highly expressed in the intercellular space after carcinogenesis of clear cell renal cell carcinoma, indicating an increase in its secretion after carcinogenesis. This application reveals the role and mechanism of exosomal PD-L2 in the development of clear cell renal cell carcinoma with or without immunity, indicates its potential as a liquid biopsy detection index for predicting the prognosis of clear cell renal cell carcinoma, and provides a theoretical basis for exosomal PD-L2 to become a therapeutic target for clear cell renal cell carcinoma.

The present invention provides a preparation method and application of a CD70-specific nano-antibody molecular imaging probe, wherein the probe includes a tumor-targeting group, a radionuclide, and a bifunctional chelator; the tumor-targeting group is a CD70-specific nano-antibody; the CD70-specific nano-antibody is R8B4, and the amino acid sequence of R8B4 is shown in SEQ ID No. 1. The probe of the present invention can realize non-invasive diagnosis of solid tumors such as renal clear cell carcinoma and hematological malignancies; and through charge adjustment, it effectively inhibits its reabsorption in the kidney, significantly reduces renal uptake, reduces nonspecific signals, improves the signal-to-noise ratio during targeted imaging or treatment, and improves imaging quality and treatment safety. This probe not only has broad application prospects in tumor diagnosis, but also provides new technical support for targeted therapy and personalized precision medicine, and has important scientific research and clinical application value.

The invention relates to application of a PELI2 gene as a molecular marker of renal clear cell carcinoma. The nucleotide sequence of the PELI2 gene is as shown in SEQ ID NO. 1. It is found for the first time that the PELI2 gene is remarkably low in expression in renal clear cell carcinoma cells, and the expression level of the PELI2 gene is closely related to prognosis of patients. The expression of the PELI2 gene in the renal clear cell carcinoma cells is remarkably reduced, and the survival rate of a renal cancer patient with high expression of the PELI2 gene is remarkably higher than that of a renal cancer patient with low expression of the PELI2 gene. Meanwhile, experiments prove that the proliferation capacity of renal clear cell carcinoma cells can be inhibited by overexpression of the PELI2 gene. On the basis, a primer pair capable of specifically recognizing the PELI2 gene and an overexpression lentivirus of the PELI2 gene are designed, and the application of the PELI2 gene as a marker in diagnosis and prognosis evaluation of the renal clear cell carcinoma and targeted therapy of the renal clear cell carcinoma is provided, which is of great significance in subsequent drug research of the renal clear cell carcinoma.

What is provided is a therapeutic agent that is effective for the treatment of ovarian clear cell carcinoma. A therapeutic agent for ovarian clear cell carcinoma includes, as an active ingredient, a proteasome inhibitor. Furthermore, in the therapeutic agent for ovarian clear cell carcinoma, the proteasome inhibitor is a substance that reversibly or irreversibly binds to a 20s β5 unit of a proteasome and inhibits a chymotrypsin-like activity. Moreover, in the therapeutic agent for ovarian clear cell carcinoma, the proteasome is a 26s proteasome. In addition, in the therapeutic agent for ovarian clear cell carcinoma, a content proportion of the proteasome inhibitor is 80% by mass or more, 90% by mass or more, or 100% by mass.

This invention provides the application of the tumor suppressor gene COTL1 in the preparation of drugs for the diagnosis and prognosis of clear cell renal cell carcinoma. This invention discloses the application of a novel tumor suppressor gene, COTL1, and its encoded protein, specifically designing the COTL1 gene and / or its encoded protein for the preparation of drugs against clear cell renal cell carcinoma; and the application of kits and methods for detecting the mRNA or protein levels of the COTL1 gene in drugs for the diagnosis and / or prognosis of clear cell renal cell carcinoma. This invention discovers that the COTL1 gene is a novel tumor suppressor gene, particularly playing an important role in the development and progression of clear cell renal cell carcinoma, providing new targets and methods for cancer diagnosis, prognosis, treatment, and drug screening.

The invention provides a urine protein composition for diagnosing renal clear cell carcinoma and application of the urine protein composition, and relates to the technical field of clinical medicine. The urine protein composition for diagnosing the clear cell carcinoma of the kidney is any one or a combination of more of IGLV3-12, CDK5RAP2, CNTNAP2, HLA-DRB3, PLA2R1, ARSL, HYDIN, KRT85, MT1H, DEFA1 and ANOS1, by determining differential urine proteins of a healthy group and a disease group and adopting the differential proteins as markers, the clear cell carcinoma of the kidney can be noninvasively, rapidly and preliminarily diagnosed, and a new direction is provided for clinical diagnosis.

The invention discloses an automatic grading and classifying method for progressive kidney cancer based on DCCD subtype markers, which comprises the following steps: taking a TGFBI gene, a PLOD2 gene and an SLC2A1 gene as marker genes of DCCD subtype renal clear cell carcinoma tissue samples subjected to clear cell differentiation to obtain an immunohistochemical staining image of a marker gene antibody corresponding to each renal clear cell carcinoma tissue sample; obtaining a staining intensity score of each immunohistochemical staining image of each renal clear cell carcinoma tissue sample; performing image segmentation and cell counting on the immunohistochemical staining image corresponding to each renal clear cell carcinoma tissue sample to obtain a positive cell proportion score corresponding to each renal clear cell carcinoma tissue sample; classifying the renal clear cell carcinoma tissue sample as a progressive renal clear cell carcinoma patient or a non-progressive renal clear cell carcinoma based on the DCCD score; according to the invention, rapid and accurate screening of progressive renal clear cell carcinoma patients is realized, the realization mode is simple, and the cost is low.

The invention provides a construction method of an advanced high metastatic renal clear cell carcinoma mouse model, which comprises the following steps: implanting Renca cancer cells into a renal capsule of a mouse, suturing a wound, and detecting colonization of tumor cells. The invention also provides a construction method of the mouse model for radical operation of renal clear cell carcinoma, and the method comprises the following steps: implanting Renca cells into a renal capsule of a mouse, suturing a wound, and detecting colonization of tumor cells; and performing a radical renal resection operation on the mouse, and continuing to detect the colonization of the tumor cells in the mouse. The method is high in success rate and easy to operate. The constructed advanced high metastatic clear cell renal carcinoma mouse model and the constructed clear cell renal carcinoma radical operation mouse model can be used for screening drugs for treating clear cell renal carcinoma.

Provided herein are methods and compositions for reducing the expression and / or activity of an oncogenic transfer RNA (tRNA). Composition for treating cancer in the subject are disclosed, comprising an inhibitor of an oncogenic transfer RNA (tRNA) to a subject in need thereof, wherein the oncogenic tRNA comprises an inhibitory nucleic acid such as ARG-TCT-4-1, an siRNA, an shRNA, an miRNA, an antisense oligonucleotide, or a nucleic acid modification such as a locked nucleic acid, a phosphorothioate modification, a 2′—O-methyl modification, a 2′—O-methoxyethyl modification, a 2′-fluoro modification, a phosphorodiamidate modification, or a mesylphosphoramidate modification. The disclosed compositions are disclosed as treating cancers such as a sarcoma, a glioblastoma, an adrenocortical carcinoma, a cholangiocarcinonma, a melanoma, a glioma, a diffuse glioma, a mature B cell neoplasm, a non-small cell lung cancer, an esophagogastric adenocarcinoma, a pheochromocytoma, a hepatocellular carcinoma, an endometrial carcinoma, a pancreatic adenocarcinoma, a breast carcinoma, an invasive breast carcinoma, a head and neck squamous cell carcinoma, a bladder urothelial carcinoma, a colorectal adenocarcinoma, an ovarian epithelial tumor, a prostate adenocarcinoma, a cervical squamous cell carcinoma, a renal non-clear cell carcinoma, or a renal clear cell carcinoma.

The application belongs to the field of biological medicine, and discloses a targeting HLA-G / CD70 bispecific CAR-T cell and application thereof. The inventors obtain a mutant with significantly improved affinity to HLA-G by mutating the natural receptor ILT4 protein of HLA-G, so that the HLA-G single-target CAR-T constructed by the mutant has stronger tumor killing ability. The bispecific CAR-T cell constructed by using the ILT4 mutant as the HLA-G binding domain and connecting the CD70 binding domain can efficiently cover tumors with high expression of HLA-G / CD70, such as heterogeneous renal clear cell carcinoma, overcome tumor antigen heterogeneity, strengthen the targeted synergistic killing efficiency, eliminate the self-killing defect of the CAR-T cell, delay the exhaustion and apoptosis of the CAR-T cell in the body, and long-term inhibit tumor recurrence.