147 results about "Stage melanoma" patented technology

The present invention belongs to the technical field of cancer immunotherapy, and particularly relates to a cholesterol-modified cationic liposome tumor vaccine, a preparation method therefor, and use thereof. In order to solve the problems of poor targeting and strong side effects of TLR agonists in anti-tumor treatment, the present invention provides a cationic liposome prepared from a cholesterol-modified 1V209 molecule, a cationic lipid component, cholesterol, and DSPE-PEG2000, and then the cationic liposome and ovalbumin 5 form the tumor vaccine by electrostatic adsorption. Animal experiments show that the vaccine can induce antigen-specific CD8+ T cells, activate lymphocytes, and generate stronger antigen cross-presentation, more memory T cells, antibodies, and cytokines. Prophylactic inoculation with the vaccine can significantly delay the progression of mouse melanoma and lymphoma and prolong the survival of mice. The combination use of the vaccine and a PD-1 checkpoint inhibitor can further enhance the anti-tumor effect. Therefore, the vaccine is a promising cancer vaccine.

The invention discloses a zinc-selenium doped white calcium stone injectable hydrogel for treating melanoma and a preparation method of the zinc-selenium doped white calcium stone injectable hydrogel. The preparation method comprises the following steps: 1, preparing hydrophilic zinc-selenium doped white calcium stone; 2, preparing oxidized sodium alginate; and (3) dispersing the hydrophilic zinc-selenium-doped white phosphorus calcium stone into the oxidized sodium alginate solution, adding the carboxymethyl chitosan solution, and uniformly mixing to obtain the zinc-selenium-doped white phosphorus calcium stone injectable hydrogel for treating melanoma. The injectable hydrogel prepared by the invention has good injectability, self-healing property and biocompatibility, and is suitable for tumor wound models with any shape and depth; the composition has good effects of promoting normal cell proliferation and inhibiting tumor cell growth, and can be used for tumor postoperative treatment to inhibit tumor recurrence and promote surgical defective tissue repair.

The invention belongs to the field of probiotics and application thereof, and particularly relates to a humanized bifidobacterium animalis probiotic strain and application thereof in preparation of drugs for preventing or treating melanoma. The preservation number of the humanized bifidobacterium animalis is GDMCC No: 65044, the preservation unit is called GDMCC for short, and the active metabolite of the humanized bifidobacterium animalis contains mannose. The composition contains the bifidobacterium animalis probiotic strain, and contains / does not contain metabolites of the bifidobacterium animalis probiotic strain and one or more physiologically acceptable excipients or carriers. The method has the advantages that the protective strain lacked by the melanoma patient is screened and separated from the intestinal tract of a healthy person, the strain can normally survive in the intestinal tract of the human body and has no toxic or side effect, and a new way is provided for prevention and treatment of the melanoma patient by supplementing the lacked protective strain and active metabolites of the patient in a targeted manner; and an innovative solution is provided for auxiliary immunotherapy of melanoma.

The application provides a radionuclide nanohydrogel microneedle and a preparation method and application thereof, and belongs to the field of nanobiomedicine. 32 P-labeled calcium phosphate, which is formed by a biomimetic reaction of Ag2S@Ca 32 P nanoparticles, and a base layer which is a base matrix and comprises hyaluronic acid 32 P nanohydrogel microneedle can release Ag2S nanoparticles in response to a weakly acidic tumor environment, and under the irradiation of near-infrared light, the photothermal conversion efficiency can effectively kill bacteria, effectively improve the tumor hypoxic environment, enhance the treatment effect of radionuclides, play an antibacterial and wound healing promoting role in melanoma defect repair, and maximize the inhibition of tumor growth and tumor recurrence.

The invention provides a method of treating a melanoma comprising (i) identifying a patient having a PD-L1-negative melanoma and (ii) administering to the patient a combination of an anti-PD-1 antibody or an antigen-binding portion thereof and an anti-CTLA-4 antibody or an antigen-binding portion thereof. The methods of the invention can extend progression-free survival for over 8 months and / or reduces the tumor size at least about 10%, about 20%, about 30%, about 40%, or about 50% compared to the tumor size prior to the administration.

The invention discloses a tumor targeting boron-containing Fe3O4-based nano-enzyme and a preparation method and application thereof, and belongs to the technical field of tumor treatment.The tumor targeting boron-containing Fe3O4-based nano-enzyme takes boron-10 doped Fe3O4 nano-enzyme as a boron-containing drug group and an enzyme activity center, and the surface of the tumor targeting boron-containing Fe3O4-based nano-enzyme is modified with a targeting group; the targeting group is chitosan-folic acid-polyethylene glycol. The tumor targeting boron-containing Fe3O4-based nano-enzyme has relatively strong selective enrichment capacity on tumor cells such as melanoma, shows good biocompatibility and low toxicity, and has relatively strong apoptosis induction and killing effects on the melanoma cells in boron neutron capture therapy; meanwhile, active oxygen free radicals can be generated in boron neutron capture therapy to generate an oxidative damage effect.

The invention discloses a spleen-targeted nano platform construction method suitable for tumor vaccination, and particularly relates to the field of vaccines.The spleen-targeted nano platform construction method comprises the steps that S1, CL15H6-DOPS LNPs, spherical polymer vesicles and erythrocyte membrane coated nano-particles are selected as spleen-targeted nano-carriers; s2, integrating an immunologic adjuvant; mn < 2 + > doped LNPs, ultrasonic response lipidosome and a CD3 antibody are selected to be coupled to serve as an integration material; s3, delivering in vivo; animal models are selected for in-vivo delivery and curative effect verification, and B16F10 melanoma mice, MC38 colon cancer mice and non-human primates are selected as the animal models respectively. By optimizing the chain length and the surface topological structure (such as spherical polymer vesicles) of the liposome, the spleen enrichment rate is remarkably increased, and the red marrow myeloid cell uptake efficiency is enhanced. By combining with common delivery of a manganese adjuvant, an STING channel is activated, secretion of type I interferon is promoted, and the proportion of antigen-specific CD8 + T cells and the tumor inhibition rate are increased.

The invention discloses a preparation method of drug-loaded membrane protein bionic vesicles based on a microfluidic technology and application of the drug-loaded membrane protein bionic vesicles to targeted melanocyte delivery drugs, and belongs to the technical field of pharmaceutical preparations. The method is easy and convenient to operate, assembly of the phospholipid bilayer and insertion of the membrane protein are accurately controlled through the laminar focusing technology, and the stable and efficient drug-loaded membrane protein bionic vesicle is formed. The drug-loaded membrane protein bionic vesicles can effectively target melanocytes, promote the uptake of the vesicles, significantly improve the accumulation of drugs in the melanocytes, and enhance the treatment effect on melanocyte related diseases (such as hyperpigmentation, melanoma, vitiligo and the like). Meanwhile, the drug-loaded bionic vesicles constructed by the invention have relatively low keratinocyte uptake rate, drug uptake of non-targeted tissues is effectively reduced, and side effects of drugs are reduced, so that the drug-loaded membrane protein bionic vesicle system constructed by the invention has great prospects in the aspect of treating melanocyte related diseases.

The application discloses a kind of elastin-like polypeptide V 20 K 40 L, mRNA vaccine and preparation method and application in preparation tumor prevention, mitigation or treating drug.The elastin-like polypeptide carrier V 20 K 40 L provided by the application has good biocompatibility, and has no adverse reaction in vivo.The elastin-like polypeptide V 20 K 40 L provided by the application has amphiphilic structure, can be loaded Melan-A mRNA by hydrophobic self-assembly and electrostatic adsorption, and is in the state of shrinkage when higher than Tt temperature, which can prevent the uncontrollable leakage of mRNA.Furthermore, V 20 K 40 L contains lysosome escape peptide, which can further improve the transfection efficiency of mRNA by promoting lysosome escape.The elastin-like polypeptide V 20 K 40 L in the application can deliver Melan-A mRNA efficiently and safely, and realize the prevention and treatment of melanoma.

A series of 1, 3, 5-triazine compounds that exhibit potent inhibition of endosomal trafficking and autophagy is provided. These compounds effectively suppress cancer cell proliferation, growth, and migration, induce cell cycle arrest at the G0 / G1 phase, promote cancer cell death via non-apoptotic pathways, and inhibit tumor sphere formation. Moreover, select compounds within this series demonstrate significant inhibition of tumor growth and metastasis in mouse models of lung cancer and melanoma. Additionally, they modulate macrophage polarization and the tumor microenvironment by regulating cytokine secretion. These findings highlight the potential of 1, 3, 5-triazine compounds as promising antitumor agents.

The invention discloses an application of an OH2 oncolytic virus combined with a PD-1 inhibitor in preparation of an antitumor drug. The OH2 oncolytic virus and the PD-1 inhibitor are jointly applied to tumor treatment, and through the synergistic effect of the OH2 oncolytic virus and the PD-1 inhibitor, the anti-tumor immune response is enhanced, and the treatment effect is improved. According to the combined treatment scheme, tumor cells can be directly killed, recurrence and metastasis of tumors can be inhibited by activating systemic immune response, and a new treatment choice is provided for tumor patients. In the application, the neutrophile granulocyte number level in the blood of a tumor patient is closely associated with the treatment effect of the anti-tumor medicine, the anti-tumor medicine can be used for evaluating the treatment effect, and the anti-tumor medicine is suitable for common tumor adaptations including colorectal cancer, esophageal cancer, head and neck tumor, gastric cancer, biliary tract system tumor, sarcoma, melanoma and other tumors.

The pharmaceutical composition for preventing and treating melanoma comprising K-ras-specific activated T cells according to the present invention uses, as an antigen composition, K-ras mutant (G12D, G12V, and G13D) recombinant overlapping peptides which are designed such that the peptides are sequentially divided into a total of 12 epitopes (n=1 to 12, wherein the last epitope (n=12) comprises 23 amino acids) in units of 30 amino acids in the amino acid sequence of K-ras with 15 amino acid sequences overlapping between the epitopes, and thus has the advantage of being more effective in recognizing and killing melanoma in which K-ras, K-ras mutant G12V, K-ras mutant G12D, or K-ras mutant G13D is detected. Therefore, the pharmaceutical composition for preventing and treating melanoma comprising K-ras-specific activated T cells according to the present invention has the advantage of being capable of effectively preventing and treating melanoma in which not only K-ras but also K-ras mutants are detected.

Here, the inventors have developed a spectral flow cytometry assay to measure heme biosynthesis. By using this new assay on melanoma cell lines, they observed a direct correlation between high PPIX levels in differentiated MITFhigh cells and a protection against ferroptosis. Conversely, cell lines with low PPIX levels were associated with a dedifferentiated MITFlow phenotype enriched in stem cell markers and more sensitive to ferroptosis inducers. They also found that inhibition of PPIX biosynthesis in differentiated melanoma cells synergizes with iron overload to induce lipid peroxidation and tumor cell death. Finally, they show that decreased levels of PPIX linked to increased ferroptosis sensitivity can be acquired in vivo in melanoma tumors that relapse after anti-MAPK targeted therapies. The present invention relates to a method of determining whether a subject has or is at risk of having melanoma ferroptosis sensitivity and targeted therapy resistance comprising i) determining the level of protoporphyrin IX (PPIX) in a biological sample obtained from the subject and ii) comparing the level determined at step i) with a predetermined reference value: wherein if the level of the PPIX determined at step (i) is lower than the predetermined reference value is indicative that the said patient is having melanoma ferroptosis sensitivity and targeted therapy resistance or wherein if the level of the PPIX determined at step (i) is higher than the predetermined reference value is indicative that the said patient is having melanoma ferroptosis resistance and targeted therapy sensitivity. The present invention also relates to a method for treating resistant melanoma in a subject in need thereof comprising a step of administering said subject with a therapeutically effective amount of a ferroptosis inducer.

The invention discloses jellyfish polypeptide with tyrosinase inhibitory activity and application of the jellyfish polypeptide, and belongs to the technical field of biology. A jellyfish crude polypeptide is prepared, a jellyfish polypeptide GEPINPEAWLWYYKYVG is identified and optimized from the jellyfish crude polypeptide, and experiments prove that the jellyfish polypeptide provided by the invention can inhibit the activity of tyrosinase in vitro, can inhibit melanin secretion of B16-F10 mouse melanoma cells, and can inhibit the activity of tyrosinase in the cells. Therefore, the jellyfish polypeptide can be used as a tyrosinase inhibitor and an anti-melanin synthesis agent and is applied to the fields of cosmetics, medical treatment and the like. Experiments prove that the jellyfish polypeptide provided by the invention has no cytotoxicity, is derived from ocean, and has no disease risks and religious barriers of terrestrial animals.

The present invention relates to the field of biomedicine, and in particular to immunogenic cell death-enhancing nanovesicle hydrogels and their applications. The present invention provides a 3D-printable, multifunctional, synergistic immunogenic cell death-enhancing nanovesicle hydrogel. The hydrogel uses SerMA hydrogel as a matrix and encapsulates cell membrane nanovesicles (N@ILO) loaded with the photothermal agent IR1061, the chemotherapy drug OXA, and the tumor acidic microenvironment regulator Lon. The hydrogel triggers initial tumor immunogenic cell death through the photothermal effect, further enhances the ICD effect through OXA, and modulates the acidic tumor microenvironment through Lon to increase T cell activity, achieving multimodal synergistic anti-tumor therapy after surgery. The hydrogel also possesses excellent photocurable 3D printing capabilities and can be used to construct personalized filling structures that match postoperative defect areas. The hydrogel has broad application prospects and provides a new strategy and theoretical basis for the comprehensive postoperative treatment of choroidal melanoma.

Disclosed are neuronal nitric oxide synthase (nNOS) inhibitors and methods of using the same in treating a disease or disorder associated with nNOS activity, such as a neurological disease or disorder, or melanoma.

The present invention relates to an antibody or fragment thereof specifically binding to meningeosis carcinoma-specific antigen, such as DDX53, KIF3C, and AKR1A1, an anti-body or fragment thereof for use in the prophylaxis and / or treatment of cancer, preferably melanoma, further preferably melanoma with leptomeningeal spread, highly preferably melanoma with meningeosis carcinomatosa, a pharmaceutical composition comprising said antibody or fragment thereof, a nucleic acid encoding said antibody or fragment thereof, a vector comprising said nucleic acid, a prokaryotic or eukaryotic host cell comprising said vector, and to a method for the prophylaxis and / or treatment of cancer, preferably melanoma, further preferably melanoma with leptomeningeal spread, highly preferably melanoma with meningeosis carcinomatosa, in a living being, comprising the admin- istration of a prophylactically and / or therapeutically effective amount of said antibody or fragment thereof or said pharmaceutical composition.

The application discloses a Daphnane type macrocyclic diterpenoid compound with a 4,7-oxygen bridge structure and a preparation method and application thereof. The monomer compound is obtained by repeatedly separating and purifying an ethyl acetate part extract of Daphne giraldii by using various separation fillers and separation technologies. The new compound is subjected to structural identification by using various 1D and 2D nuclear magnetic resonance spectrometry and high resolution mass spectrometry (HR-ESI-MS) and the like, and a molecular formula and a structural formula thereof are deduced. Further in-vitro cell activity researches show that the Daphnane type macrocyclic diterpenoid compound with the 4,7-oxygen bridge structure separated from the Daphne giraldii has good inhibitory activity on melanoma cells. The application is helpful to development and utilization of natural compounds of the Daphne giraldii.

The invention belongs to the technical field of new applications of medicines, and particularly relates to an aniline pyridine TEAD degradation agent, a preparation method thereof and an application of the degradation agent in preparation of antitumor drugs. According to the research, a novel aniline pyridine TEAD degradation agent with a clear structure is designed and synthesized by coupling a TEAD palmitoylation inhibitor niflumic acid serving as a lead compound with a CRBN type E3 ligase ligand through connecting chains with different lengths and different types by virtue of a computer-aided drug design means. The influence of the optimal compound (XY-3L) on cancer cell proliferation and cell functions is detected in an in-vitro cell experiment, and the curative effect of the optimal compound (XY-3L) in a melanoma lung metastasis model is explored in vivo.

Provided herein are activated adoptive T-cell compositions targeting plasma cell dyscrasias such as multiple myeloma and methods of treating plasma cell dyscrasias such as multiple myeloma using such compositions. The T-cell compositions of the present disclosure are activated against a select group of antigens associated with multiple myeloma (MMAAs) and, in certain embodiments, in combination with more widely expressed tumor associated antigens (TAAs). In particular, the T-cell compositions of the present disclosure are directed to the MMAAs selected from B-cell maturation antigen (BCMA), X box Protein 1 (XBP1), CS1, and Syndecan-1 (CD138), or a combination thereof. In certain embodiments, the T-cell composition includes T-cells activated to a TAA selected from preferentially expressed antigen of melanoma (PRAME), Survivin, Wilms' Tumor 1 protein (WT1), and melanoma antigen 3 (MAGE-A3), or a combination thereof.

The present invention provides an antibody or an antigen-binding fragment thereof with binding specificity for human interleukin-1 receptor accessory protein (IL1RAP) wherein the antibody or antigen-binding fragment is capable of inhibiting the binding of antibody ‘CAN04’ to human IL1RAP. The invention further provides the use of such antibodies or an antigen-binding fragments in the treatment and / or diagnosis of IL-1 associated diseases and conditions, including cancers such as acute myeloid leukemia and melanoma.

The application discloses a melanoma data enhancement method based on image fusion, which comprises the following steps: acquiring a melanoma data set and uniformly sizing images in the melanoma data set; traversing the uniformly sized images, and performing the following operations on each image: cutting the image in half to obtain two cut images; randomly flipping one of the two cut images, denoting the randomly flipped cut image as a first image and the cut image without random flipping as a second image; randomly acquiring a ratio number in the range of [0, 1], and fusing the first image and the second image according to the ratio number to form a fused image; and saving all the fused images to complete data enhancement of the images in the melanoma data set. The method realizes image data enhancement by fusing the cut images according to the ratio number, so as to balance data categories, expand data volume, improve model robustness and accurately identify melanoma.

The invention belongs to the technical field of medicines, and particularly relates to application of temozolomide bromide as a sound-sensitive agent, and the temozolomide bromide has a structure shown in a formula (I). The invention provides a novel preparation and purification scheme of the sound-sensitive agent temozolomide bromide, and compared with traditional temozolomide, the product has a better killing effect on tumor cells, and has an extremely remarkable killing effect on the tumor cells and cell cycle arrest under the ultrasonic synergistic effect. The temozolomide derivative has a low toxicity effect similar to that of temozolomide on normal neuronal cells at low concentration, and animal experiments prove that the temozolomide derivative can penetrate through a blood-brain barrier. In addition, the invention has immeasurable clinical application value in the treatment of tumors, especially glioma and / or melanoma.

Disclosed are preparation and anti-tumor application of a gene therapy vector interfering CKLF-like MARVEL transmembrane domain-containing protein 6 (CMTM6) expression. Specifically, disclosed are a gene therapy vector encoding a gene sequence targeting CMTM6 and a derivative thereof, a gene sequence encoded by a vector, a preparation method, and a use of a vector alone and in combination with other drugs in treating tumors. These gene therapy vectors comprise adeno-associated viruses and lentiviruses, etc., can inhibit the expression of CMTM6 in tumor tissues, can effectively inhibit the in-vivo growth of mouse and human colorectal cancer, melanoma, liver cancer, breast cancer, non-small cell lung cancer and the like by improving the tumor immunosuppression microenvironment, exhibit a strong anti-tumor effect in combination with immune checkpoint antibodies, chemotherapeutic drugs, immunoagonistic drugs, and metabolic regulation drugs, and have significant efficacy on PD-L1-deficient tumors and immune checkpoint antibody drug-resistant tumors.

This invention discloses a (4-oxopent-1-ynyl)(diphenylcyclohexylphosphine) gold (I) and its application in the preparation of drugs for treating melanoma, belonging to the field of biomedicine. This invention provides a novel (4-oxopent-1-ynyl)(diphenylcyclohexylphosphine) gold (I) that effectively combats melanoma by inhibiting the proliferation and growth of melanoma cells, with low side effects. It can serve as a candidate drug for treating melanoma-related diseases caused by various factors, showing promising application prospects in the development of innovative drugs for melanoma treatment. It provides a new drug option for the treatment of melanoma and can alleviate the problems of relatively limited current treatment options and drug resistance.

The invention provides an engineered whole-cell vaccine as well as a preparation method and application thereof. The engineered cell comprises a tumor cell and attenuated salmonella loaded in the tumor cell. According to the engineered cell disclosed by the invention, the attenuated salmonella can activate an NF-kappa B pathway and drive macrophages in tumor cells to be reprogrammed from an immunosuppression phenotype M2 to an immunogenicity phenotype M1, and the reprogrammed M1 type macrophages can enhance presentation of specific tumor antigens in the tumor cells; therefore, the immune microenvironment of macrophages can be remodeled, the immune response to the melanoma is enhanced, and the prevention and treatment effects on postoperative recurrence and metastasis of the melanoma are further improved.

The invention discloses a composition with a tumor mitochondrial dual regulation effect, temperature-sensitive hydrogel and application, and belongs to the technical field of biological medicine, the composition is composed of a peroxide initiator and a mitochondrial autophagy inhibitor, the peroxide initiator is used for causing mitochondrial damage, and the mitochondrial autophagy inhibitor is used for causing mitochondrial autophagy. The mitochondrial autophagy inhibitor is used for inhibiting mitochondrial The peroxide initiator is indocyanine green, chlorin, iron oxide nanoparticles or Fe-MOFs (Metal-Organic Frameworks); the mitochondrial autophagy inhibitor is chloroquine, 3-methyladenosine or bajulomycin A1; the tumor is specifically melanoma; the combination of the peroxide initiator and the mitochondrial autophagy inhibitor can better inhibit the energy metabolism of tumor cells and inhibit the occurrence and development of tumors, and after the composition is delivered through the temperature-sensitive hydrogel carrier, the treatment effect of the composition on tumors is further improved.

The invention provides application of lactobacillus rhamnosus H23A017 combined with trametinib in preparation of drugs for treating melanoma, lactobacillus rhamnosus H23A017 is combined with MEK inhibitor trametinib in an intratumoral injection mode, it is found that compared with a single medication group, combined treatment can improve the expression level of IFN-gamma and TNF-alpha in a tumor microenvironment, and the effect of treating melanoma is achieved. The application has the advantages that tumor cell apoptosis is promoted, tumor cell infiltration is increased, the tumor volume is further reduced, and a new strategy is provided for development of low-toxicity and high-efficiency melanoma immune drug combination.

The invention relates to the technical field of biological medicine, in particular to biodegradable magnesium sustained-release hydrogel, a preparation method thereof and application of the biodegradable magnesium sustained-release hydrogel in preparation of tumor postoperative adjuvant therapy products. The hydrogel is prepared by taking carboxymethyl chitosan and sodium alginate as matrixes, loading 1.2-9g of metal magnesium powder, mixing, adjusting pH and fumigating and cross-linking with glacial acetic acid, and a three-dimensional network of the hydrogel can realize continuous and controllable release of magnesium ions. According to the invention, the dual functions of promoting wound healing and removing residual tumor cells are realized: magnesium ions are used as healing-promoting enzyme cofactors to accelerate wound repair, and meanwhile, oxidative stress is induced to play an anti-tumor role by disturbing tumor cell iron metabolism; different release rates can be realized by regulating and controlling the loading amount of the magnesium powder, and different tumor postoperative treatment requirements are met. The hydrogel is excellent in biocompatibility, can be completely degraded, is suitable for postoperative adjuvant therapy of solid tumors such as melanoma and breast cancer, can reduce systemic toxic and side effects and tumor drug resistance risks, and is large in clinical transformation potential.

The application provides application of a C1q neutralizing monoclonal antibody combined with a PD-1 monoclonal antibody in preparation of a drug for treating a solid tumor, and belongs to the technical field of biological medicine. It is found that the combination of the C1q neutralizing monoclonal antibody and the PD-1 monoclonal antibody can effectively enhance the anti-tumor effect on the solid tumor, and especially exhibits a significant synergistic inhibitory effect on the growth and metastasis of a solid tumor resistant to the PD-1 monoclonal antibody, wherein the solid tumor resistant to the PD-1 monoclonal antibody includes but is not limited to colorectal cancer, melanoma, lung adenocarcinoma and liver cancer. The application provides a new treatment option for patients resistant to the PD-1 monoclonal antibody, and has a wide clinical application prospect.