216 results about "Immune checkpoint" patented technology

The present invention provides a combination of (i) an immune checkpoint modulator and (ii) a T-cell redirecting multifunctional antibody, or an antigen binding fragment thereof, for use in therapeutic treatment of a cancer disease. The T-cell redirecting multifunctional antibody comprises (a) a specificity against a T cell surface antigen; (b) a specificity against a cancer- and / or tumor-associated antigen; and (c) a binding site for human FcγRI, FcγRIIa and / or FcγRIII, wherein the antibody, or the antigen binding fragment thereof, binds with a higher affinity to human FcγRI, FcγRIIa and / or FcγRIII than to human FcγRIIb.

The invention discloses application of a TEAD1 palmitoylation inhibitor VT103 in preparation of a PD-1 immune checkpoint antibody sensitization drug, and belongs to the technical field of tumor immunotherapy. It is confirmed for the first time that TEAD palmitoylation inhibition can overcome immunotherapy drug resistance of MSS tumors by regulating and controlling the state of the microsatellite, a brand new action target is provided for clinical development of immune checkpoint inhibitor sensitizing drugs, microsatellite instability is induced firstly, then immunotherapy is carried out in a combined mode, and therefore the treatment effect is improved.

The invention discloses a method for enhancing mechanical force of CAR-T cells on target cells to overcome mechanical immune checkpoints of SFs and application, and relates to the technical field of crossing of immunotherapy and biomechanics, in particular to CAR-T cells targeting fibroblast activated protein. The invention discloses a CAR-T (chimeric antigen receptor T-T) cell and SFs (small-form-factor s) DNA (deoxyribonucleic acid) nano connector for connecting the CAR-T cell with the SFs, the formation of a CAR cluster and mechanical force transmission are promoted by shortening the membrane spacing of an immune synaptic interface to 16-28nm, the DNA nano connector is formed by self-assembling complementary tetrahedral DNA structures, and the TDS comprises a single-stranded DNA vertex S4 with the length of 24-58 nucleotides. According to the method for enhancing the mechanical force of the CAR-T cells on the target cells to overcome the mechanical immune checkpoints of the SFs and the application, the escape and killing problems of the soft target cells are solved, the soft target cells are efficiently removed, and the killing rate of the CAR-T cells treated by DNJ-17 on the SFs is remarkably increased.

Described herein are gene features that provide prognosis, diagnosis, treatment and molecular subtype classification of cancer by genomic and epigenomic profiling, including immune checkpoint regulators such as Programmed Death Ligand 1 (PDL-1). Using the methods and compositions described herein, specific and sensitive detection of biomarkers of interest is provided. Such biomarkers indicate disease pathogenesis, which provides opportunities for selection of treatments, including treatment regimens intended to overcome tolerance mechanisms.

This invention relates to the application of exosomes in reversing tumor resistance to immune checkpoint (PD-1) inhibitors. A novel application of exosomes in the preparation of pharmaceutical compositions reversing tumor resistance to immune checkpoint inhibitors is disclosed. Exosomes generated from tumor cells recombinantly expressing adenylate cyclase 7 (ADCY7) can significantly reverse tumor resistance to PD-1 inhibitors, and the exosomes exhibit a synergistic effect with the PD-1 inhibitors.

The present invention discloses an antitumor pharmaceutical composition based on immune checkpoint blockade and its application, which comprises paroxetine hydrochloride and a T cell enhancer, which is at least one of vitamin E and thymosin. Through a series of in vitro and in vivo experiments, the present invention has first discovered that cannabidiol and paroxetine hydrochloride can effectively reduce the expression of PD-L1 on the surface of tumor cells, block the PD-1 / PD-L1 signaling pathway, and enhance the tumor cell killing effect of T cells. Based on this, the addition of a T cell enhancer can further increase the number and activity of T cells, significantly enhancing the killing ability of T cells after immunosuppression is released, thereby significantly enhancing the antitumor effect of the drug. The components of the pharmaceutical composition of the present invention, cannabidiol, paroxetine hydrochloride, vitamin E, and thymosin, exert a synergistic effect, improving the antitumor effect.

The present application relates to the technical field of biopharmaceuticals, and in particular, polypeptides or derivatives thereof, pharmaceutically acceptable salts thereof based on artificial intelligence design and applications thereof are provided, wherein the amino acid sequence of the polypeptides is shown as SEQ ID NO:1.The polypeptides or derivatives thereof, pharmaceutically acceptable salts thereof can simultaneously bind to PD-1 and CTLA-4, can effectively block the binding between PD-1 and CTLA-4 and their ligands respectively, release the inhibition of immune checkpoint proteins PD-1 and CTLA-4 on immune cells, and significantly enhance the anti-tumor immune response of the body. The polypeptides or derivatives thereof, pharmaceutically acceptable salts thereof can be used for detecting PD-1 and / or CTLA-4, and can also be used for treating or preventing diseases related to PD-1 and / or CTLA-4.

A method is provided for treating a subject with cancer using a recombinant polypeptide comprising a DRα1 domain containing a glutamine residue at the position corresponding to amino acid 45 of SEQ ID NO: 1 or SEQ ID NO: 2, or an antigenic peptide covalently bound to a portion thereof. In some cases, the subject has a tumor that is resistant to immune checkpoint blockade treatment and / or does not express a BRAF mutation. The present invention provides, for example, a method for treating a subject with cancer, comprising administering to the subject a therapeutically effective amount of a recombinant polypeptide comprising a DRα1 domain containing a glutamine residue at the position corresponding to amino acid 50 of SEQ ID NO: 1 or SEQ ID NO: 2, or an antigenic peptide covalently bound to a portion thereof; or a nucleic acid encoding the recombinant polypeptide.

The application discloses application of DUSP4 in preparation of a marker for predicting the curative effect of immunotherapy of hepatocellular carcinoma and a sensitizing drug, and belongs to the technical field of biological medicine.The application finds that high expression of dual specificity phosphatase 4 (DUSP4) is significantly related to high response rate and long survival period of an immunological checkpoint blocking therapy for a hepatocellular carcinoma patient.DUSP4 promotes CD8+ T cell and NK cell infiltration and remodels an immune microenvironment by inhibiting a TGF-beta signal path, down-regulating an immunosuppressive factor and up-regulating an antigen presenting molecule and a chemotactic factor.The application provides a kit and a method for detecting the expression level of DUSP4 to predict an immunotherapy response, and a combined drug composition comprising a DUSP4 activator or a TGF-beta inhibitor and an immunological checkpoint inhibitor.Experiments prove that up-regulation of the expression of DUSP4 can significantly enhance T cell killing function, and produces a synergistic anti-tumor effect with an anti-PD-1 antibody.The application provides a new strategy for precise stratified treatment and overcoming immunological drug resistance of hepatocellular carcinoma.

The present invention relates to a method for detecting immuno-checkpoint blockade (ICB)-induced hypophysitis or a risk thereof in a living organism, a test kit for carrying out the method and a method for treating and / or prophylaxis ICB-induced hypophysitis or a risk thereof in a living organism.

The present disclosure relates to compositions and methods for inhibiting tumor evasion by reducing immune checkpoint suppression. In some embodiments, provided herein are compositions that block the interaction between PD-1 and its ligand (e.g., PD-1 and / or PD-L2) while promoting the interaction of the cells on which PD-1 and its ligand are expressed. Also provided are methods of using such compositions.

An antibody or antibody derivative having a higher immune checkpoint inhibitory effect. The antibody or antibody derivative is capable of enhancing immune activity against cancer cells, and can be used to treat cancer. The antibody is a heterodimeric antibody or antibody derivative capable of binding to both the TIM-3 and CD39 antigens. The heterodimeric antibody or antibody derivative is capable of enhancing immune activity against cancer cells.

A method of selecting a treatment for a subject having cancer is disclosed. The method comprises:(a) determining a level of catalytic activity of at least one DNA repair enzyme in a biological sample of the subject; and(b) selecting an immune checkpoint regulator as a treatment for a subject having a statistically significant different level of catalytic activity of the DNA repair enzyme as compared to the catalytic activity of the DNA repair enzyme in a biological sample of a healthy subject.

The present invention is directed to selected anti-PD-1 antibodies capable of binding to both cynomolgus monkey PD-1 and to human PD-1: PD-1 mAb 1, PD-1 mAb 2, PD-1 mAb 3, PD-1 mAb 4, PD-1 mAb 5, PD-1 mAb 6, PD-1 mAb 7, PD-1 mAb 8, PD-1 mAb 9, PD-1 mAb 10, PD-1 mAb 11, PD-1 mAb 12, PD-1 mAb 13, PD-1 mAb 14, or PD-1 mAb 15, and to humanized and chimeric versions of such antibodies. The invention additionally pertains to PD-1-binding molecules that comprise PD-1 binding fragments of such anti-PD-1 antibodies, immunocongugates, and to bispecific molecules, including diabodies, BiTEs, bispecific antibodies, etc., that comprise (i) such PD-1-binding fragments, and (ii) a domain capable of binding an epitope of a molecule involved in regulating an immune check point present on the surface of an immune cells. The present invention also pertains to methods of using molecules that bind PD-1 for stimulating immune responses, as well as methods of detecting PD-1.

The present invention provides: a pharmaceutical composition for preventing, alleviating or treating cancer, comprising a compound of chemical formula 1 or 2, which is a pyrazole derivative, or a pharmaceutically acceptable salt, solvate, stereoisomer or combination thereof; and a pharmaceutical composition for preventing, alleviating or treating cancer, comprising a compound of chemical formula 1 or 2, or a pharmaceutically acceptable salt, solvate, stereoisomer or combination thereof, and an immune checkpoint inhibitor or an immune checkpoint pathway inhibitor.

This invention discloses an engineered CAR-T cell targeting HIF-1α and its application in tumor immunotherapy. The CAR-T cell expresses a chimeric antigen receptor regulated by the hypoxia-responsive element HRE promoter, with its extracellular domain specifically binding to HIF-1α and its intracellular domain employing the 4-1BB+CD3ζ signaling module. Simultaneously, through immune checkpoint knockout and cytokine / chemokine modification, it achieves hypoxia-dependent activation, anti-exhaustion, high infiltration, and strong killing effects. The CAR-T cells of this invention significantly improve the adaptability to the solid tumor microenvironment and therapeutic efficacy, reduce off-target toxicity, and can be used to prepare drugs for treating malignant tumors such as lung cancer, liver cancer, pancreatic cancer, colorectal cancer, and glioblastoma, possessing significant clinical translational value.

The present application relates to the technical field of polymer chemistry, and particularly relates to a responsive dendritic polyamino acid modified polyurethane and a preparation method and application thereof.The responsive dendritic polyamino acid modified polyurethane has a structure shown in formula I.The responsive dendritic polyamino acid modified polyurethane provided by the present application can specifically expose positive dendritic polylysine in the unique acidic environment of tumor tissue, trigger immunogenic death of tumor cells, release tumor antigens, and comprehensively activate an anti-tumor immune response.Meanwhile, the positive dendritic polylysine causes an increase in reactive oxygen species (ROS) of tumor cells, oxidizes a diselenium bond in the polyurethane into selenic acid, reduces the expression of immune checkpoints of tumor cells, reverses the immunosuppressive microenvironment of tumor tissue, realizes synergistic treatment of immune activation and reversal of the tumor immunosuppressive microenvironment, and realizes a better tumor immunotherapy effect.

The present disclosure describes methods and compositions involving using LRRK2 mutations as biomarkers for the prediction of immune checkpoint response in cancer and methods and compositions for treating cancers having certain LRRK2 mutations in a subject.

A method of treating cancer in a subject that includes administering in situ to the cancer of the subject a therapeutically effective amount of a plant virus or plant virus-like particle in combination with administration of an immune checkpoint therapy to the subject.

The application discloses a kind of nanomaterial and its preparation method and application, the nanomaterial includes exosome and liposome;The exosome expresses immune checkpoint, the exosome is derived from brain glioma cell;The liposome is loaded with I type photosensitizer.The application is by PDT, immune checkpoint and brain glioma cell exosome antigen three tubes simultaneously to remodel tumor local immune microenvironment, greatly improve the efficiency of cancer immunotherapy, can activate strong anti brain glioma immune response and overcome immune escape.

This invention discloses an antibody-engineered bone marrow stromal cell and its applications, belonging to the field of biomedical technology. Using bone marrow stromal cells as a biological carrier, this invention externally modifies them with immune checkpoint antibodies to form an antibody-coated engineered cell preparation, thereby achieving targeted and precise mitochondrial delivery of exhausted T cells. This cell preparation can be used in combination with other immunotherapies that can induce T cell exhaustion, such as tumor immunotherapies and CAR-T therapy, to help enhance their anti-tumor efficacy and duration of effect.

Described herein are gene panel compositions and methods of use thereof for spatial omic analysis in biological samples. The gene panels may be organized into distinct modules that target various aspects of immune response, tumor biology, and intercellular communication within the microenvironment. These methods involve spatial omic techniques, such as spatial transcriptomics, to localize gene expression across tissue sections, providing detailed insights into immune cell infiltration, immune checkpoint activation, and tumor-immune interactions. The disclosed compositions and methods are applicable for diagnostics, monitoring therapeutic responses, and guiding personalized treatment strategies. The modular design of the gene panels allows for customization based on specific research or clinical objectives.

Provided herein are methods and compositions for the treatment of cancer by modulating the microbiome to enhance the efficacy of immune checkpoint blockade. The microbiome may be modulated by the administration of butyrate and / or butyrate-producing bacteria. Also provided herein are methods of determining a response to an immune checkpoint inhibitor by identifying if a subject has a favorable microbial profile.

The application discloses a pancreatic cancer immunotherapy drug composition for jointly targeting CD96 and PD-1, relates to the technical field of biological medicine, and comprises an anti-human CD96 blocking antibody and an anti-human PD-1 blocking antibody. By jointly blocking the double immune checkpoints of CD96 and PD-1, the pancreatic cancer immunotherapy drug composition presents a significant synergistic effect compared with single antibody treatment, can effectively enhance the killing activity of T cells on pancreatic cancer cells, reverses the immune suppression microenvironment of pancreatic cancer, and restores the anti-tumor immune response of the body. The in-vivo experimental results show that the drug composition can significantly inhibit the growth of transplanted tumors, reduce the tumor volume and the tumor weight, and the tumor inhibition effect is obviously better than that of a single drug group. The preparation has stable properties and simple administration, and provides a safe and effective new immunotherapy scheme with a conversion application prospect for clinically refractory pancreatic cancer.

The invention provides a polypeptide for inhibiting tumor immune escape and application thereof. The polypeptide is a peptide derived from 181-190 amino acids at the amino terminal of ubiquitin specific protease 15 (USP15), enters tumor cells by means of a cell-penetrating peptide CPP, and can obviously block the combination of USP15 and PD-L1 in the tumor cells, promote ubiquitination degradation of PD-L1, obviously lower the level of tumor cells PD-L1, inhibit tumor immune escape and play an in-vitro and in-vivo anti-tumor role. In addition, when the U10 polypeptide and the PD-1 monoclonal antibody (mAb) are jointly applied to a mouse body, the effect of synergistically resisting tumor immune escape is achieved. Therefore, the U10 polypeptide can be used as a new strategy of immune checkpoint blocking treatment, is used for tumor immunotherapy, and has important clinical application value.

Embodiments of the present disclosure relate to a composition that comprises a recombinant plasmid (RP) with a sequence of nucleic acids. The sequence comprise a start region, an end region and an insert positioned between the start region and the end region. The insert encodes for a sequence of micro interfering ribonucleic acid (miRNA) that may be complimentary to a sequence of target messenger RNA (mRNA) that encodes for translation of a target biomolecule. The miRNA can cause the target mRNA to be degraded or inactivated, thereby causing a decrease in bioavailability of the target biomolecule because it is degraded or inactivated by the miRNA, thereby decreasing the bioavailability of the target biomolecule. In some embodiments of the present disclosure, the target biomolecule is an immune checkpoint protein.

The invention discloses a protease cleavable liposome and application thereof in treating colon cancer. The preparation method of the protease cleavable liposome comprises the following steps: synthesizing functional peptide from cancer homing peptide, protease cleavable protein fragments and lysine; the preparation method comprises the following steps: reacting a functional peptide with difunctional polyethylene glycol COOH-PEG2000-Mal, and covalently linking the obtained product with DSPE-NHS to obtain a protease cleavable material; and coupling the aPDL1 antibody to a protease cleavable material to obtain the protease cleavable liposome. The protease cleavable liposome can activate cytokines to kill tumor cells, so that effective endocytosis by colon cancer cells is realized, and an immune checkpoint blocking effect is achieved. Therefore, the protease cleavable liposome not only can be used as an effective delivery carrier for immune checkpoint blocking treatment, but also can be used as a universal platform for colon cancer immunochemistry combined treatment. The method has an important application value.

Provided are compositions and methods for treating Lewis Y antigen positive cancers in mammalian subjects by administering an effective amount of a radionuclide-labeled Lewis Y antigen targeting agent such as an antibody labeled with an alpha particle-emitting radionuclide such as 225Ac. The methods may further include administration of additional agents, such as radiosensitizing agents, immune checkpoint therapies, CD47 blockades, and / or DNA damage response inhibitors.