342 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 provides an immunodetection method of a multi-index immune checkpoint detection kit, which belongs to the technical field of immunodetection and comprises three main stages of sample preparation, immune reaction and data analysis. The method comprises the following steps: firstly, carrying out centrifugal separation to obtain a plasma sample, and preparing a fluorescent microsphere coupled capture antibody and biotin labeled detection antibody compound; then carrying out immune reaction, forming a sandwich type immune complex through specific binding, and adding streptavidin marked by phycoerythrin for signal amplification. Detecting a fluorescence signal by adopting a flow cytometer to obtain an original data matrix; a contribution feature vector, a utility feature vector and an expression feature matrix are extracted through a feature decomposition algorithm, and a deep learning model of a total-score-total structure is established for data analysis. Finally, a detection report containing a quantitative result, an importance score and reliability evaluation is generated, and the technical problem that in the prior art, the analysis accuracy of a multi-index immune checkpoint detection result is insufficient is solved.

The invention belongs to the technical field of engineered probiotics, and particularly relates to engineered probiotics for radiosensitization and tumor metabolism regulation as well as a preparation method and application of the engineered probiotics. The engineering probiotics comprise probiotics and core-shell type metal nanoparticles which are loaded on the probiotics and are synthesized through a biological directional mineralization effect; the core of the core-shell type metal nanoparticle is a palladium element, and the outer layer of the core-shell type metal nanoparticle is a palladium element and a gold element. The engineering probiotics provided by the invention have excellent enzyme catalysis performance and can target and retain in tumor sites, and through the synergistic effect of all components in the engineering probiotics, adenosine metabolism is effectively inhibited, secretion of pro-inflammatory cytokines is enhanced, tumor microenvironment is promoted to be converted into an inflammatory state, up-regulation of immune checkpoints is inhibited, and the immune checkpoints are inhibited. And T cells are inhibited from being transformed into depletion phenotype and transformed into effect type from depletion type. After the SBRT and the immune checkpoint inhibitor are combined for use, the growth of tumors can be effectively inhibited, and the effect of enhancing immune radiotherapy is achieved.

The invention provides application of TRMT61A and its inhibitor tetramethylthiuram disulfide in tumor immunotherapy, and relates to the technical field of biological medicine, clinical research proves that RNA m1A methyltransferase TRMT61A is highly expressed in tumor tissues and is related to poor prognosis of tumor patients, and can be used as one of tumor therapy targets. Meanwhile, high expression of the TRMT61A is related to poor prognosis of a tumor patient receiving anti-PD-1 immunotherapy, and after anti-PD-1 antibody immunotherapy is carried out on the patient with low TRMT61A expression level in the tumor of the patient, pathological complete relief is easier. Tetramethylthiuram disulfide inhibits TRMT61A, inhibits m1A modification regulation of TRMT61A on PD-L1 mRNA, increases PD-L1 protein expression, and is combined with a PD-1 antibody drug to significantly enhance the immunotherapy effect of the anti-PD-1 immune checkpoint drug in treating malignant tumors.

Provided are an immune checkpoint inhibitor containing as an active ingredient a substance that inhibits the interaction of integrin and immunosuppressive receptor (referred to hereinafter as LILR) B3 and a therapeutic agent for immune checkpoint-related disease containing as an active ingredient a substance that inhibits the interaction of integrin and LILRB3.

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 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.

The invention relates to a selenized microalgae preparation and application thereof in preparation of immune preparations for treating tumors. The microalgae are induced and cultured in a selenium-rich solution for several days, and then are collected and injected to the tumor site to inhibit the growth of the tumor site. The preparation process of the selenized microalgae is simple, and the selenized microalgae can stimulate an organism to generate strong immune response, activate dendritic cells and T cells and regulate an immunosuppressive microenvironment at a tumor through various pathways such as NF-kappa B, so that an efficient and long-term tumor suppression effect is realized; meanwhile, the microalgae can enhance immune checkpoint blocking treatment, and a certain foundation is laid for combined application of microorganism-mediated immunotherapy and immune checkpoint blocking.

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.

Provided are an activity-regulatable IL-12 fusion protein and the use thereof. The fusion protein comprises a first structural unit, a second structural unit, and a third structural unit. The first structural unit is selected from a first Fc fragment, or a first antibody or an antigen-binding fragment thereof, wherein the first antibody or the antigen-binding fragment thereof has the binding activity to a tumor antigen or an immune checkpoint; the second structural unit is selected from a cleavable linker or a non-cleavable linker; and the third structural unit comprises an IL-12 cytokine or a functional fragment thereof. The second structural unit mediates the steric hindrance of the first structural unit to mask the activity of the IL-12 cytokine in the third structural unit, thereby reducing the toxic side effects of in-vivo use of the IL-12 cytokine. Compared with a wild-type IL-12, the fusion protein has the advantage of high safety, and can be further fused with an antibody Fab, scFv or VHH, an antigen-binding peptide or a recombinant protein, a polypeptide, etc. to obtain a multifunctional fusion protein that can be conditionally released and activated.

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.

Described herein are compositions comprising a lanthanide (III) modified fatty acid and methods of treating cancer with the composition. In particular, the application includes a lanthanide (III) modified fatty acid is a 9-R′, 10-R″ tri octadecanoate compound. This lanthanide (III) modified fatty acid can be combined with additional therapeutic agents, such as chemotherapeutic agents, radiopharmaceuticals, hormone therapies, CDK inhibitors, epigenetic modulators, selective estrogen receptor modulators, selective estrogen receptor degraders, aromatase inhibitors, phosphatidyl inositol-3-posphate kinase inhibitors, ATP-adenosine axis-targeting agents, signal transduction inhibitors, RAS signaling inhibitors, PI3K inhibitors, arginase inhibitors, HIF inhibitors, AXL inhibitors, PAK4 inhibitors, immunotherapeutic agents, immune checkpoint inhibitors, and agonists of stimulatory or co-stimulatory immune checkpoints.

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 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.

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.

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.

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 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.

Two major treatment strategies employed in fighting non-small cell lung cancer (NSCLC) are tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). The choice of strategy is based on heterogeneous biomarkers expressed by the lung tumor tissue. A major challenge for molecular testing of these biomarkers is the insufficiency of biopsy specimens from patients with advanced NSCLC. Disclosed herein is a method for predicting a response to immune-checkpoint blockade immunotherapy. The method generally involves imaging the subject with positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with computed tomography to produce 18F-FDG PET / CT images of the tumor, analyzing the images using PET, CT, and Kulbek Leibler Divergence statistical (KLD) features or, alternatively using deep leaning such as Neural Networks; generating a radiomic signature from the identified features or Network characteristics; and computing a radiomic score based on the radiomic signature that is predictive of responsiveness to ICIs or TKIs.

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.

Provided is a composition capable of enhancing the effect of an antibody drug such as an immune checkpoint inhibitor, etc. A β-glucan is used as an active ingredient of a composition for enhancing the effect of an antibody drug. This composition is used suitably for antibody drugs that have an effect of suppressing growth of cancer via immune checkpoint inhibition; e.g., antibody drugs including a monoclonal antibody to PD-L1.

Nanoparticles are provided having a calcium core, such as calcium hydroxide (Ca (OH) 2) and calcium carbonate (CaCO3) particles. The nanoparticles may further include a shell, such as a shell formed from silica or oleic acid. The nanoparticles may further include a coating, such as a coating formed from polyethylene glycol, and optionally further include a coating of lipids. The nanoparticles may further include a targeting agent, such as a targeting agent that targets dendritic cells, T cells, or other immune cells. The nanoparticles may further include or otherwise be used in combination with an active agent, optionally selected from the group consisting of an antigen, a chemotherapeutic drug, an immune system modulator or an immune checkpoint modulator. Also provided are pharmaceutical compositions comprising the nanoparticles and methods of use thereof for increasing an immune response against, for example, cancer and infection.

The application belongs to the technical field of biological medicine, and particularly relates to preparation and application of a self-assembled nanocomposite based on a CRISPR / Cas9 system and ursolic acid. The nanocomposite takes UA self-assembled nanodrug UA NPs as a core, and is co-assembled with low-molecular-weight protamine LMWP having good cell penetration capacity and a CRISPR / Cas9 plasmid pTIM3 for knocking down TIM3 to form a nanocomposite ULP NPs. The nanocomposite prepared in the application can be enriched at a tumor site through EPR effect, and can reach the effect of enhancing liver cancer immunotherapy by knocking down the inhibitory immune checkpoint TIM3. The regulation characteristics and molecular mechanism of the UA NPs as a self-assembled general template for delivering the CRISPR / Cas9 system to inhibit the immune checkpoint TIM3 are disclosed, and the application has a wide application prospect in liver cancer immunotherapy.

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.