278 results about "Paclitaxel" patented technology

The invention relates to the field of natural products, in particular to a dimer compound of guaiane type sesquiterpenes and uric acid as well as an extraction and separation method and application of the dimer compound. According to the invention, a new dimer compound of guaiane type sesquiterpene and uric acid is extracted and separated from carpesium abrotanoides in Guizhou, and it is found that the dimer compound has relatively strong anti-tumor activity. The compound has strong inhibitory activity on breast cancer, prostate cancer, nasopharynx cancer, liver cancer, lung cancer, leukemia, pancreatic cancer, glioma, osteosarcoma, skin cancer, cervical cancer, ovarian cancer, kidney cancer and esophageal cancer, and provides an optional scheme for broad-spectrum anti-cancer drugs. Moreover, in human prostate cancer cells PC3, human cervical cancer cells Hela, human liver cancer cells HepG2 and human glioma cells U87 which are resistant to paclitaxel, the compound also shows strong anti-cancer activity, which indicates that the compound has the potential of treating patients resistant to paclitaxel.

Methods of treating a central airway obstruction (CAO), benign airway stenosis, asthma, chronic obstructive pulmonary disease (COPD), or an airway tumor in a human subject, methods of treating chronic rhinosinusitis (CRS) or chronic rhinosinusitis with nasal polyps (CRSwNP) in a human subject, methods of treating a eustachian tube disorder in a human subject, and devices and systems for performing the methods. A method of treating a central airway obstruction (CAO), benign airway stenosis, asthma, chronic obstructive pulmonary disease (COPD), or an airway tumor in a human subject includes inserting a drug-coated balloon catheter into a target site in a trachea, mainstem bronchus, bronchus intermedius, lobar bronchus, segmental bronchus, or sub-segmental bronchus, wherein the balloon is coated with a coating layer including the therapeutic agent and one or more additives. The therapeutic agent includes paclitaxel, sirolimus, or a derivative thereof. The method includes inflating the balloon to dilate the airway and deliver a therapeutic agent to the airway wall. The method includes deflating the balloon. The method also includes withdrawing the balloon catheter from the target site.

The invention discloses an OTX-015 (Ox-015) loaded cascaded responsive nano particle and a preparation method thereof. The nanoparticle has a three-layer core-shell structure, wherein the innermost layer is a cross-linked nanoparticle of chitosan and paclitaxel; the middle layer is a polydopamine layer loaded with a bromodomain inhibitor OTX-015; the outermost layer is a gelatin layer grafted with babali; wherein the cross-linked substance of the chitosan and the paclitaxel is a cross-linked substance containing a disulfide bond. The invention also provides a preparation method of the cascade responsive nano-particle and application of the cascade responsive nano-particle in preparation of an antitumor drug targeted delivery system. The nanoparticle provided by the invention improves the tumor microenvironment while activating in-vivo autoimmunity, and kills tumor cells by using photothermal therapy assisted chemotherapy drugs, so that the synergistic effect of chemotherapy / photothermal therapy / immunotherapy is realized, and a new idea is provided for clinical tumor treatment.

The invention discloses an SERS (Surface Enhanced Raman Scattering) detection method for paclitaxel drug concentration in blood of a breast cancer patient, and belongs to the technical field of detection. The method comprises the following steps: performing acetonitrile two-step precipitation centrifugal treatment on a blood sample to obtain a detection sample; the method comprises the following steps: constructing a high-sensitivity SERS substrate (the volume ratio of gold nanoparticles to ethanol is 1: (90-100), and a film is formed on a water-cyclohexane interface) through self-assembly of gold nanoparticles on a liquid-liquid interface; the method comprises the following steps: dropwise adding a sample into a substrate, and detecting characteristic peaks of 1024cm <-1 > and 1053cm <-1 > by using a portable Raman spectrometer (785nm, 30mW, 0.5 s); and calculating the paclitaxel concentration in combination with a pre-established quantitative curve. The method is easy and convenient to operate and suitable for clinical bedside rapid monitoring.

The invention discloses a compound liposome, a freeze-dried powder injection as well as a preparation method and application of the freeze-dried powder injection. The compound lipidosome comprises a lipidosome membrane and an inner water phase encapsulated in the lipidosome membrane, the paclitaxel palmitate is encapsulated in a lipid bilayer of the liposome membrane; the gemcitabine or the salt thereof is encapsulated in the inner water phase; the compound liposome comprises the following raw materials: paclitaxel palmitate, lecithin, a polyethylene glycol derivative, gemcitabine or a salt thereof, an organic solvent and a buffer solution A; the molar ratio of the lecithin to the polyethylene glycol derivative is 1: (0.01-0.15). The compound liposome disclosed by the invention is relatively high in encapsulation efficiency (especially the encapsulation efficiency of PTX-PA is relatively good) and relatively high in safety, the preparation method is simple and easy to operate, the industrialization degree is high, and the prepared compound liposome has a relatively good long-circulation effect, a relatively good anti-tumor effect and good in-vivo tolerance.

Many drugs useful in treating cancer are metabolized by CYP2C8 enzymes, by CYP3A4 enzymes, or both. The effects of concomitant administration of relacorilant and paclitaxel, a drug used to treat cancer that is a substrate for both CYP2C8 and CYP3A4, are disclosed herein.Relacorilant potently inhibited CYP2C8 and CYP3A4 in in vitro tests, indicating that co-administration of relacorilant and paclitaxel would increase paclitaxel plasma exposure more than 5-fold in vivo, requiring significant reductions in paclitaxel doses when co-administering paclitaxel with relacorilant.Surprisingly, paclitaxel plasma exposure increased only by about 80% instead of the expected more than 5-fold increase expected with concomitant relacorilant and paclitaxel administration. Applicant discloses safe methods of co-administering relacorilant and paclitaxel by reducing the dose of paclitaxel to about half the paclitaxel dose used when paclitaxel is administered alone. Relacorilant and such reduced doses of paclitaxel may be co-administered to treat cancer, e.g., ovarian or pancreatic cancer.

The invention belongs to the technical field of medicines, and discloses preparation and application of a paclitaxel-loaded liposome nano targeting preparation. The paclitaxel-entrapped nano-particles are prepared by adopting a film dispersion method, and micromolecular hyaluronic acid is entrapped on the surfaces of the lipid nano-particles by utilizing the charge effect. The bionic nano-drug provided by the invention is helpful for solving the problems of poor solubility, low bioavailability, high toxicity and the like of the anticancer drug paclitaxel. The hyaluronic acid has affinity with a glycoprotein CD44 receptor on the surface of a tumor cell, so that the nanoparticles are targeted and concentrated at a tumor part, the anti-tumor effect is improved, and the systemic toxicity of paclitaxel is reduced. The preparation process is simple, the cost is low, the stability is good, the repeatability is high, and the preparation method also has a better development prospect in the aspect of clinical application transformation.

The invention relates to the technical field of medical instruments, in particular to a paclitaxel drug coating balloon dilatation catheter and a preparation method and application thereof.The paclitaxel drug coating comprises a substrate layer, a middle layer and an outer layer; the substrate layer comprises paclitaxel and a hydrophilic excipient; the middle layer comprises a lipophilic excipient and a temperature response type polymer; and the outer layer comprises a pH sensitive polymer. The substrate layer is combined with the surface of the balloon, so that excellent conveying stability is provided, the medicine is effectively prevented from falling off prematurely in the conveying process of the catheter, and the firmness of the coating is improved; a micropore network structure is formed in the middle layer, the network structure is expanded under the body temperature condition, the porosity is increased, slow release of the medicine is achieved, the absorption amount of the medicine on the blood vessel wall is effectively increased, and the medicine effect time is prolonged; the solubility of the outer layer is improved in a slightly acidic blood vessel wall environment, so that the release of the medicine is further promoted, and the effective release of the medicine on the blood vessel wall is ensured.

The invention belongs to the technical field of pharmaceutical preparations. The invention discloses a multifunctional bionic nano preparation, a preparation method and application. According to the multifunctional bionic nano preparation, the ginsenoside Rg3 has the dual functions of a medicine and a membrane stabilizer, the platelet membrane has the natural targeting capability on circulating tumor cells and metastases, and meanwhile, the cationic liposome is used for adsorbing negatively-charged NETs nucleic acid protein compounds, so that potential reversal and active targeting are achieved, and the multifunctional bionic nano preparation has a good application prospect. And by co-carrying paclitaxel (PTX) and a photothermal agent (PCP) and integrating photothermal-chemotherapy-immunogenic death (ICD) induction functions, the tumor-related fibroblast activation can be effectively inhibited, circulating tumor cells can be efficiently captured, a tumor immune microenvironment can be remodeled, the tumor cells can be effectively killed, and tumor distal metastasis can be inhibited.

The invention provides application of a CHD1L detection reagent in preparation of a drug-resistant breast cancer screening kit, and belongs to the field of biological medicine. Researches find that when the CHD1L gene expression level in cancer tissues of a breast cancer patient is high, the breast cancer patient is prone to drug resistance to paclitaxel drugs, and the treatment effect of the paclitaxel drugs is poor. The reagent for detecting the CHD1L gene expression level is used for preparing the drug-resistant breast cancer screening kit, can be used for auxiliary diagnosis of clinical breast cancer types, provides an effective basis for related treatment measures or decisions of patients, and has a good clinical application prospect.

The application discloses a drug-loaded micelle capable of effectively crossing the blood-brain barrier, which is an amphiphilic conjugate composed of a reduction-sensitive paclitaxel prodrug and a nucleic acid complex, wherein the reduction-sensitive paclitaxel prodrug is used as a hydrophobic part, and the nucleic acid complex is used as a hydrophilic part, and the drug-loaded micelle is self-assembled in an aqueous environment; the reduction-sensitive paclitaxel prodrug is formed by the reaction of paclitaxel and a disulfide bond-containing linker; and the nucleic acid complex is formed by connecting an antisense oligonucleotide and an interfering RNA through a DNA bridge. The drug-loaded micelle exhibits superior blood-brain barrier penetration, effectively realizes enrichment in brain tumors, solves the problem of low blood-brain barrier penetration efficiency of existing nano-carriers, and provides an effective basis for brain drug delivery and brain diseases such as brain tumor imaging and treatment.

The invention discloses a protein drug loaded GelMA microsphere, a preparation method and application thereof, the protein drug loaded GelMA microsphere comprises a GelMA microsphere and a protein drug loaded on the GelMA microsphere, and the protein drug is composed of albumin paclitaxel and alphaPD-L1. The drug carrier is loaded with albumin paclitaxel and the alphaPD-L1 antibody, so that synergistic treatment can be realized, and the cancer treatment effect is improved; gelMA is used as a drug carrier, albumin paclitaxel and an alphaPD-L1 antibody are delivered, and the drug-loaded GelMA microspheres are injected into tumor tissues in situ, so that the targeting property and bioavailability of the drug can be effectively improved, side effects are reduced, the drug is enriched in a focus, and the circulating drug concentration is reduced.

The application belongs to the technical field of biological medicine, and particularly relates to a nano delivery system based on exosome membrane fusion and a preparation method and application thereof, which comprises: (1) a prodrug complex formed by paclitaxel (PTXL) and IR780; (2) a liposome core loaded with the prodrug complex, and a membrane material of the liposome core comprises: DSPE-PEG-MAP, DSPE-PEI, phospholipid and cholesterol; and (3) a homologous tumor cell-derived exosome membrane fused to the surface of the liposome core. The application realizes the design of multi-level delivery in the same nanoparticle by means of the optimization of the properties of the liposome membrane composition, the fusion of the exosome and the liposome membrane, the mixed biomimetic nanoparticle particle size, the preparation of the PTXL targeted prodrug and the like, so as to improve the treatment effect at different levels.

The application provides a combination drug of a PLA2G7 inhibitor and a chemotherapeutic drug and its use in resisting triple-negative breast cancer, and belongs to the technical field of medicines. The combination drug is a PLA2G7 inhibitor and a chemotherapeutic drug in the same or different specifications of unit preparations for simultaneous or separate administration, and a pharmaceutically acceptable carrier. The application first discovers and proves that the PLA2G7 inhibitor Darapladib can significantly enhance the anti-tumor activity of paclitaxel, 5-fluorouracil or cisplatin on triple-negative breast cancer, and meanwhile, the combination of the PLA2G7 inhibitor and paclitaxel has a synergistic effect in down-regulating the phosphorylation level of STAT3 protein in cancer cells and inhibiting the growth and proliferation of cancer cells; the combination of the PLA2G7 inhibitor and 5-fluorouracil also shows a synergistic effect in inhibiting the growth and proliferation of cancer cells. The application provides a new and effective combination drug strategy for improving the treatment effect of the chemotherapeutic drug on triple-negative breast cancer.

The invention relates to the technical field of biological medicines, in particular to application of dauricine in preparation of medicines for inhibiting ovarian cancer SKOV3 cell proliferation and treating ovarian cancer. The invention finds that dauricine has a remarkable inhibition effect on drug-resistant ovarian cancer cells, the dauricine has a clear dose-dependent relationship on the inhibition activity of the ovarian cancer cells SKOV3 in a concentration range of 1-50 mu M, and the IC50 value is 2 mu M. Meanwhile, the effect of inhibiting SKOV3 cell proliferation of the dauricine can be remarkably improved by combining the dauricine with paclitaxel or 5-fluorouracil. Therefore, dauricine can be used for preparing medicines for inhibiting ovarian cancer SKOV3 cell proliferation and improving ovarian cancer multidrug resistance, and has a good clinical application prospect.

The application provides a zwitterionic polypeptide modified paclitaxel derivative, a prodrug nanocarrier micelle and a preparation method thereof, and belongs to the field of biological medicines. The preparation method comprises the following steps: mixing a zwitterionic polypeptide containing a sulfhydryl group with 2,2'-dithiodipyridine in a polar solvent, stirring and reacting, crystallizing, and obtaining a polypeptide derivative containing a disulfide bond; and then dissolving the polypeptide derivative and a sulfhydrylated paclitaxel (PTX-SH) in a polar solvent, adding glacial acetic acid to adjust the pH, stirring and reacting, and obtaining the paclitaxel derivative. The paclitaxel derivative is used for preparing a prodrug nanocarrier micelle by loading a hydrophobic anticancer drug, the prodrug nanocarrier micelle has a long blood circulation time in the body, a high drug loading capacity, small toxic side effects, excellent glutathione response and fast on-demand controlled release characteristics, and good tumor inhibition effect.

Treatments of cancers involve a wide range of treatment. The current invention relates to chemotherapy of tumors using taxanes, in particular docetaxel. More in particular it relates to a method for the treatment of a cancer in a patient comprising orally administering an effective dose of docetaxel, whereby side effects are controlled by preventing peak plasma levels of docetaxel that induce said side effects, whilst maintaining an effective plasma level of docetaxel to eradicate tumor cells.

The invention relates to application of a KRT7-AS inhibitor in preparation of a medicine for treating ovarian cancer or paclitaxel drug resistance of the ovarian cancer. The invention discloses a mechanism of KRT7-AS for promoting ovarian cancer progression by inhibiting ferroptosis for the first time. After KRT7-AS is knocked down by utilizing an shRNA (short hairpin ribonucleic acid) inhibition technology, biological behaviors of ovarian cancer cells and ovarian cancer paclitaxel drug-resistant cells are influenced: proliferation, migration and invasion capabilities are reduced to different degrees, and meanwhile, ferroptosis is activated to inhibit tumor growth. The invention provides a new thought and a potential target for precise treatment of ovarian cancer, and is expected to bring good news to ovarian cancer patients. Long-chain non-coding RNA KRT7-AS is novel carcinogenic lncRNA of ovarian cancer, and the effect of KRT7-AS knockout in the ovarian cancer cell process is researched. By targeting KRT7-AS, ferroptosis of ovarian cancer cells is regulated and controlled, so that tumor progression is influenced. The KRT7-AS inhibitor is used for targeting KRT7-AS, can be used as a treatment method for treating ovarian cancer, and is an innovative strategy for treating ovarian cancer.

The present application relates to a kind of ganoderma lucidum spore as carrier paclitaxel ganoderma lucidum spore oil self-nanoemulsion composite microparticle and its preparation method, belong to medical technology field.The pretreated ganoderma lucidum spore (GLS) is obtained by process screening, and it is used as drug carrier, and the paclitaxel ganoderma lucidum spore oil self-nanoemulsion (PGS) is loaded therein, and paclitaxel composite microparticle (PGS@GLS) is obtained.Release curve in vitro shows that PGS@GLS has the characteristics of slow release after reaching intestinal tract;In vivo pharmacodynamics experiment shows that PGS@GLS can significantly inhibit the development and metastasis of colorectal cancer in mice;Tumor tissue section immunofluorescence analysis shows that PGS@GLS can effectively exert the therapeutic effect on colon cancer.Paclitaxel self-nanoemulsion ganoderma lucidum spore composite microparticle promotes cancer immune cycle by inducing immunogenic cell death and immune regulation, significantly improves the treatment effect of colon cancer, and has good biological safety.

A kind of epirubicin prodrug, albumin nanoparticle pharmaceutical composition comprising the prodrug and its preparation method and application.The long-chain fatty acid is connected with epirubicin by using acyl hydrazone bond sensitive to tumor acid microenvironment to construct epirubicin prodrug, so as to improve the binding capacity of epirubicin and albumin.The prepared epirubicin prodrug can realize the sufficient dissolution of prodrug using water as solvent, then mixed with albumin aqueous solution, and after high pressure homogenization, the uniformly distributed epirubicin-fatty acid prodrug albumin nanoparticle pharmaceutical composition can be obtained.The preparation process provided does not need to use organic solvent, breaks through the technical obstacle that existing albumin preparation product must use organic solvent to prepare, simplifies the preparation process, and at the same time avoids the risk of organic solvent residue and inducing albumin denaturation.

The invention provides a preparation method of a polymer nanorod with a controllable and adjustable length-diameter ratio. The invention further provides a preparation method of the anti-tumor nano-drug, the anti-tumor nano-drug is prepared by the preparation method of the polymer nano-rod with the controllable and adjustable length-diameter ratio, and the paclitaxel nano-drug is prepared by the method. The three-step method adopted by the invention is based on a traditional emulsification method, special instruments and equipment are not needed, large-scale production is easy to realize, and the batch yield is relatively high; the preparation conditions are mild, and the drug activity can be effectively protected; the method is low in energy consumption, economical and efficient. According to the method, the length-diameter ratio of the nanorod can be controllably adjusted on the basis of not changing the raw material composition of the nanorod, the consistency of other parameters in the subsequent biological behavior research is favorably kept, the influence of mixed factors is reduced, and the reliability and repeatability of the research can be improved. Besides, when the length-diameter ratio of the nano-carrier is adjusted, only the process of heating fracture in the last step needs to be changed, so that the cost can be greatly saved, customized production is facilitated, or preclinical simple preparation is realized.

A taxane supramolecular nanocomposite. The supramolecular nanocomposite comprises a taxane active substance, including but not limited to paclitaxel, docetaxel, and cabazitaxel, as well as a self-assembling carrier, a high molecular polymer, and a dissolution promoter. The dissolution promoter may comprise one or more of alcohols, polybasic organic acids, and amino acids. Also disclosed are a preparation method and use of the supramolecular nanocomposite. The supramolecular nanocomposite is suitable for oral administration and topical application, providing effects such as increased local drug exposure concentration and efficacy, reduced systemic side effects, etc.

The invention discloses a nucleolin aptamer modified carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system as well as a preparation method and application thereof, and relates to the field of tumor treatment. The nucleolin aptamer AS1411 is coupled with glycolysis regulation nano-particles through covalent bonds, and the carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system comprises a carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system, a carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system and a carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system, the glycolysis regulation nano-particles take carboxymethyl chitosan as a carrier skeleton, the carrier skeleton is loaded with a lonidamine derivative through grafting modification, and the nano drug delivery system can synchronously entrap paclitaxel. According to the invention, a synergistic treatment system integrating active targeting, metabolic regulation and chemotherapy is constructed, and by virtue of a multi-mechanism synergistic effect, an antitumor drug for inhibiting tumor cell activity, glycolysis or tumor metabolism reprogramming is prepared; the huge potentials of overcoming the drug resistance bottleneck of traditional chemotherapy, enhancing the curative effect and reducing the toxic and side effects are shown.

The present application belongs to the technical field of medicine, and particularly relates to albumin nanoparticles co-loading paclitaxel and BMS-202, a preparation method and application thereof. The present application comprises a carrier and a delivery carrier loaded with drugs; comprises a carrier and drugs loaded by a delivery carrier; the drugs are paclitaxel and an inhibitor BMS-202 co-loaded with paclitaxel, and the delivery carrier is human serum albumin. The present application comprises the following steps: step 1: paclitaxel and the inhibitor BMS-202 are dissolved in an organic solvent as an organic phase; step 2: human serum albumin is dissolved in water as an aqueous phase; step 3: the organic phase is directly added to the aqueous phase, and after mixing, ultrasonic treatment is immediately performed to make the system form a nanoparticle suspension; step 4: the nanoparticle suspension is subjected to purification treatment to remove the organic solvent and unencapsulated drugs, and albumin nanoparticles co-loading paclitaxel and BMS-202 are obtained. The present application is applied to the preparation of esophageal squamous cell carcinoma drugs. Compared with the prior art, the present application is relatively effective and safe in the treatment of esophageal cancer.

The invention provides a pharmaceutical composition and application thereof in preparation of medicines for treating tumors. The pharmaceutical composition comprises the orbitrazine fumarate, a second active agent and pharmaceutically acceptable auxiliary materials. The second active agent comprises at least one of tamoxifen, irinotecan hydrochloride, sorafenib, cis-platinum, doxorubicin hydrochloride, paclitaxel and etoposide. The scheme provided by the invention has a remarkable synergistic anti-tumor effect, and a combined medication scheme is expected to provide a safer and more effective treatment choice for tumor patients, so that the pharmaceutical composition has an important clinical application value.

The invention discloses a cyclosporin A combined self-assembly paclitaxel nano-drug and a preparation method and application thereof, and belongs to the field of biological medicine, the cyclosporin A combined self-assembly paclitaxel nano-drug is a nano-particle which is composed of paclitaxel, cyclosporin A and zinc ions and has a regular rod-like morphology, and the particle size of the nano-particle is 1-10 micrometers. The self-assembled paclitaxel nano-drug is prepared by combining cyclosporin A on the basis of a zinc ion coordinated supramolecular self-assembly strategy, so that the stability of the nano-drug can be improved, the toxic and side effects are reduced, the killing effect on drug-resistant tumors is enhanced, the approximate biological safety is retained, and the drug-resistant tumors are prevented from being damaged. The invention provides a new thought for overcoming the current situation of drug resistance of paclitaxel, and has important research value and wide application prospect.

The application discloses a gene combination for biosynthesis of paclitaxel and application thereof, and relates to the technical field of genetic engineering. The application breaks through the limitation of traditional paclitaxel extraction and synthesis technology, and for the first time adopts a transformation method of Physcomitrella patens to perform multi-gene co-expression on a paclitaxel synthesis pathway. The application has wider gene source compatibility, and opens up a brand-new technical path for paclitaxel synthesis. As a model plant, the Physcomitrella patens has the characteristics of rapid growth and easy cultivation. After a specific gene combination is introduced into the Physcomitrella patens, a metabolic pathway related to paclitaxel synthesis in the Physcomitrella patens cells can be fully activated, and the Physcomitrella patens is prompted to efficiently synthesize paclitaxel.

The present invention provides a use of paclitaxel cationic liposomes in the manufacture of a medicament for treating terminal solid cancer, a use of paclitaxel cationic liposomes and a systemic therapeutic agent in the manufacture of a medicament for treating terminal solid cancer, and a method for treating terminal solid cancer, in which a therapeutically effective amount of paclitaxel cationic liposomes is administered to a patient with terminal solid cancer, or a therapeutically effective amount of paclitaxel cationic liposomes and a systemic therapeutic agent is administered to a patient with terminal solid cancer.

The inventors have prepared a novel anti-Cath-D antibody (F1M1) that can reduce tumor growth in a Cath-D secreting basal-like TNBC cell line with strong immune infiltration, without significant toxicity. The F1M1 antibody prevents recruitment of immunosuppressive M2 polarized tumor-associated macrophages (TAMs) and induces activation of natural killer cells in the tumor, and the F1M1 also enhances activation of antitumor M1 polarized TAM, recruitment and maturation of conventional cDC1 dendritic cells in the tumor to promote antigen presentation and reduce depletion marker expression of CD4 + and CD8 + T cells in the tumor and drainage lymph nodes. It is worthy of noting that the affinity of the antibody F1M1 to Cath-D is better than that of the antibody F1 prepared by the inventor in advance. The inventors also have prepared a novel Fc-optimized F1M1-Fc + human antibody which can promote ADCC induction of cancer cells and CAF, improve anti-tumor efficacy, and trigger recruitment, activation and cytotoxic activity of NK cells in tumors. The F1M1-Fc + F1M1-Fc + can inhibit the growth of MDA-MB-231 and SUM159 TNBC cell xenografts and two TNBC-PDX (one of the TNBC-PDX is resistant to neoadjuvant chemotherapy), and has no obvious toxicity. In addition, the F1M1-Fc < + > improves the treatment effect of the paclitaxel and enzalutamide combined medicine. Thus, the present invention relates to anti-cathepsin-D antibodies and their use in the treatment of cancer, in particular triple negative breast cancer.

The present invention provides a WRN inhibitor for use in the treatment of cancer, in particular microsatellite instability-high (MSI- H) or mismatch repair deficient (dMMR) cancer, wherein the treatment further comprises administration of: A. an ionising radiation-based therapy selected from: i) external beam radiation, ii) brachytherapy and Hi) a radiopharmaceutical, or B. carboplatin and paclitaxel; The WRN inhibitor is a compound of formula (1g) or compound C : Formula (C).