1027 results about "Immunotherapy" patented technology

The invention belongs to the cross technical field of nanomedicine, tumor treatment and immunotherapy, and particularly provides tumor mitochondria-targeted copper death selective induction nanoparticles, which are prepared by the following preparation method: S1, specifically coupling TPY and MHI through condensation reaction to obtain MTPY; s2, MTPY and copper ions are subjected to complexation, and an MTPY-Cu complex is obtained; and S3, the MTPY-Cu complex and albumin are subjected to self-assembly, and the MTPY-Cu-coated Alb nanoparticles are formed. The dosage of copper is only 1 / 1000 of that of free Cu < 2 + >, and equivalent immune regulation and killing effects can be achieved; primary tumors and distant tumor focuses can be inhibited, and lung metastasis is reduced; immune memory can be induced, and relapse can be prevented; the traditional Chinese medicine composition is combined with cis-platinum to remarkably enhance the curative effect and reverse the induced immunosuppression; the invention has the advantages of high biological safety and no obvious liver and kidney toxicity or hemolytic reaction.

The invention discloses a tumor immunotherapy curative effect prediction method and system based on multi-modal data, and the method comprises the steps: firstly, obtaining the multi-source tumor data of a patient, including pathological image data, medical image data, genome and molecular data, and clinical and demographic indexes; secondly, processing the multi-source tumor data to form a unified data set; thirdly, aiming at different modal data, adopting a corresponding feature extraction sub-network to extract each modal depth feature; then, a cross-modal attention mechanism is adopted to realize feature dynamic weighting and deep fusion, and unified multi-modal fusion representation is obtained; then, constructing a prediction model, and outputting an immunotherapy benefited population classification identification result, RECIST curative effect multi-classification prediction and survival prediction; and finally, generating a visual result and a feature contribution degree ranking of a prediction basis, and forming a clinical auxiliary decision report. According to the method, the prediction accuracy and stability can be remarkably improved, and meanwhile, the method has result interpretability and clinical application value.

The invention relates to the technical field of medical artificial intelligence, and discloses a non-small cell lung cancer immunotherapy risk assessment method and system and a storage medium, and the method comprises the steps: constructing an optimal strategy tree model capable of dividing a patient into a plurality of subgroups based on a historical patient data set, and determining an initial optimal treatment strategy for each subgroup; determining a subgroup to which a new patient belongs and an initial treatment strategy thereof according to the model; in the treatment process, the deviation degree between the individual response trajectory of the patient and the average response trajectory of the subgroup to which the individual response trajectory belongs is calculated; and when the deviation degree exceeds a preset threshold value of the subgroup, triggering an adaptive adjustment mechanism, and outputting an updated treatment suggestion. By establishing a dynamic monitoring and closed-loop feedback mechanism based on the subgroup benchmark, the technical problem that an existing scheme is difficult to carry out prospective identification and dynamic intervention on individualized risks is solved, so that the accuracy, safety and individualized level of non-small cell lung cancer immunotherapy are improved.

The invention relates to the field of image processors and biological medicines, and discloses an NK cell activity rapid detection method based on image processing. The method comprises the following steps: acquiring an unmarked time sequence phase image sequence of an NK cell and target cell co-culture system; performing cell instance segmentation to track individual cells; extracting a morphological dynamic characteristic parameter set of the target cell, wherein the morphological dynamic characteristic parameter set comprises a volume change rate, a phase gradient entropy, a cytoplasm phase fluctuation frequency and a nuclear region phase mean value; inputting the parameters into a pre-trained death state discrimination model, and outputting a death probability; and calculating a killing efficiency index based on the death probability evolution curve, and judging the activity level of the NK cells. The system comprises a phase image acquisition unit, a cell segmentation unit, a feature extraction unit, a death judgment unit and an activity judgment unit. Through unmarked imaging and deep learning fusion analysis, high-precision, real-time, quantitative and ultra-early NK cell activity evaluation is realized, and the method is suitable for clinical instant inspection and immunotherapy monitoring.

The present invention provides improved and / or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

An isolated cell having a central memory T-lymphocyte (Tcm) phenotype, the cell being tolerance-inducing cell and capable of homing to the lymph nodes following transplantation, the cell being transduced to express a cell surface receptor comprising a T cell receptor signaling module is described. Methods of generating same and using same are also described.

The invention belongs to the technical field of biological medicine, and provides CKS1B serving as an immunotherapy response prediction biomarker and application of the CKS1B, and according to the application, CKS1B serves as an immunotherapy response marker, and a CKS1B inhibitor is combined with an active component to treat a model mouse. In-vitro cell experiments are adopted to evaluate the immunotherapy prediction effect of the CKS1B as a biomarker on esophageal squamous carcinoma, a Cks1b overexpression tumor mouse model, a homologous mouse model and a human immune reconstruction mouse model are established, and a CKS1B inhibitor is combined with active ingredients to treat the two models; results show that the CKS1B inhibitor combined with the active component can promote removal of esophageal squamous carcinoma cells by CD8 + T cells, inhibit interferon signal channels and antigen presentation, effectively recover immune response, inhibit tumor cell proliferation and significantly reduce tumor volume, so as to achieve the purpose of treating esophageal squamous carcinoma.

The invention provides an organoid chip for screening micro-ecological drugs as well as application and a preparation method of the organoid chip, and relates to the technical field of biological medicines. The invention provides a chip integrating intestinal epithelium, a prostate cancer organ and a bladder cancer organ, which is used for researching how microecological preparations, such as probiotics, metabolites and the like, affect tumor microenvironment and immunotherapy effects. The chip can simulate interaction of intestinal tract-tumor axis, and provides an in-vitro evaluation system for precise tumor immunotherapy.

The invention discloses a gamma delta T cell efficient amplification method and application, and belongs to the technical field of cell biology. The amplification method comprises the following steps: separating PBMC (peripheral blood mononuclear cells) by adopting a density gradient centrifugation method, carrying out initial culture through a polylysine coated container, carrying out three-stage dynamic stimulation, combining with an X-VIVO 15 culture medium of 5-8% autoserum, and finally carrying out anti-gamma delta TCR magnetic bead separation to obtain high-purity cells. Through collaborative optimization of stepped factor combination, staged container coating and a low-serum system, the amplification multiple of the gamma delta T cells reaches 150-180 times, the purity is larger than or equal to 90% after purification, the cytotoxicity and the survival ability are remarkably improved, the gamma delta T cells can be efficiently used for immunotherapy of tumors and infectious diseases, and stable technical support is provided for clinical transformation of the gamma delta T cells.

The invention relates to the technical field of biological medicines, and discloses a PD-L1 K263 acetylation modified antibody, which is prepared from an immunogen containing a sequence as shown in SEQ ID NO.1. The PD-L1 K263 acetylation modified antibody is a PD-L1 K263 acetylation modified antibody. The invention also discloses a preparation method of the PD-L1 K263 acetylation modified antibody. The preparation method comprises the following steps: designing and synthesizing a polypeptide antigen, preparing an immunogen, immunizing animals, purifying the antibody and evaluating serum titer. The antibody provided by the invention can accurately recognize and combine with the PD-L1 protein subjected to K263 acetylation modification in the breast cancer, provides a specific tool for qualitative and quantitative detection of K263Ac-PD-L1 in the breast cancer, and provides a reliable molecular marker detection means for evaluating the curative effect of anti-PD-1 / PD-L1 immunotherapy; therefore, a biological preparation with specificity and practicability and a technical support are provided for accurate diagnosis, targeted therapy and curative effect monitoring of breast cancer.

The present invention provides improved and / or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

To provide processes for production of tumor infiltrating lymphocytes and uses of the same in immunotherapy.SOLUTION: The present invention provides improved and / or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. These TILs are found to be useful in therapeutic treatment regimens.SELECTED DRAWING: None

The invention discloses a regulation mechanism research method of depleted precursor CD8T cells, and relates to the field of immunology and molecular biology. Comprising the following steps: detecting the expression level of the ARHGAP9 gene in a chronic virus infection model; constructing a T cell specific ARHGAP9 gene knockout animal model; the influence of ARHGAP9 deletion on the frequency, phenotype and function of the Tpex cell is analyzed; a single cell transcriptome sequencing technology reveals that ARHGAP9 regulates and controls a downstream signal channel of a Tpex cell. By constructing a chronic virus infection model, detecting the expression dynamic state of the ARHGAP9 gene, knocking out an animal model by utilizing T cell specificity ARHGAP9, and combining flow cytometry, qPCR, single cell transcriptome sequencing and other technologies, the invention discloses the effect of the ARHGAP9 as a novel immune checkpoint molecule, and provides a theoretical basis for developing Tpex cell targeting immunotherapy.

This invention belongs to the field of biomedical technology, specifically relating to the discovery and application of biomarkers for predicting the efficacy of immunotherapy in nasopharyngeal carcinoma. This invention provides a reliable combination of 10-gene TLS biomarkers that can effectively predict the pathological TLS status in nasopharyngeal carcinoma tissue. This 10-gene TLS biomarker combination exhibits stable and significant prognostic predictive value: regardless of standard treatment or immunotherapy, a high TLS score can effectively identify patients with better survival outcomes (such as FFS, OS, and DMFS), providing important evidence for individualized risk assessment and treatment strategy selection.

This invention relates to the field of nanomedicine delivery systems, specifically to an ultrasound-enhanced synergistic immunotherapy drug delivery system, its preparation method, and its applications. The ultrasound-enhanced synergistic immunotherapy drug delivery system includes a lipid shell and a fluorocarbon gas encapsulated within the lipid shell. The lipid shell is made from cancer cell membranes and a lipid membrane formed from synthetic phospholipids. The lipid shell integrates a protein degradation-targeting chimera for degrading PD-L1. This invention combines targeted drug delivery, PD-L1 targeted degradation, and ultrasound enhancement technology to construct an integrated synergistic immunotherapy drug delivery system. Through multi-mechanism synergistic action, it overcomes the bottlenecks of existing PROTAC delivery systems, achieving a highly efficient anti-tumor immune response. This technical solution solves the technical problems of limited tumor tissue penetration and cellular uptake efficiency of PROTAC degrading agents targeting PD-L1, resulting in unsatisfactory delivery effects and promising prospects for widespread application.

The invention belongs to the technical field of biological medicine, and discloses an anti-CD39 nano antibody and application thereof. The anti-CD39 nano antibody has an amino acid sequence as shown in SEQ ID NO.1, 5, 9, 13, 17, 21 or 25. The anti-CD39 nano antibody of some examples has good antigen specificity, can be effectively combined with a target antigen CD39, and can effectively block or inhibit the hydrolysis of ATP (adenosine triphosphate) by the CD39, so that the depletion of T cells by a tumor microenvironment is effectively inhibited, and the curative effect of tumor immunotherapy is expected to be improved. The anti-CD39 nano antibody of some examples of the invention can further improve the curative effect of T cell immunotherapy related to CAR-T, TCR-T, TIL, TAL, NK, CIK and the like.

The present application belongs to the field of cell therapy and immunotherapy, and provides a genetically engineered human trophoblast, a preparation method and application thereof. The human trophoblast takes K562 cells as starting cells, and stably expresses membrane-bound interleukin 21, CD137 ligand and Delta-like ligand 1 after genetic engineering. The constructed K562 three-factor trophoblast can significantly improve the expansion efficiency, activation state and functional stability of NK cells and γδT cells. The synergistic mechanism includes enhancing the proliferation, cytotoxicity and stemness maintenance of NK cells and γδT cells through STAT3, NF-κB and Notch signaling pathways, respectively. The human trophoblast has the advantages of good expression stability, significant functional enhancement, and high activity after freezing and recovery.

Described herein are compositions of binding agents and carrier proteins, and optionally at least one therapeutic agent, and methods of making and using the same, in particular, as a cancer therapeutic. Also described are lyophilized compositions of binding agents and carrier proteins, and optionally at least one therapeutic agent, and methods of making and using the same, in particular, as a cancer therapeutic. Still also described are methods for treating and / or increasing the therapeutic effectiveness of an immunotherapy of a patient suffering from a cancer which expresses PD-LI or PD-L2 by administering to the patient a nanoparticle composition and a PD-I immunotherapy.

The invention specifically discloses a beta-diketone iridium complex as well as a preparation method and application thereof, and relates to the technical field of biological medicines. The beta-diketone iridium complex provided by the invention has high phototoxicity and low dark toxicity, can be applied to tumor cells as effective PSs of PDT, and is specifically delivered to the tumor cells by taking a traditional Chinese medicine monomer tripterine as a supplement in combination with a nano-targeting delivery technology for photodynamic / immune synergistic treatment of hypoxic tumors.

The invention provides a three-specificity immune cell adapter-cytokine fusion protein for malignant tumor immunotherapy as well as a preparation method and application of the three-specificity immune cell adapter-cytokine fusion protein. The fusion protein comprises a first binding domain, a second binding domain and a cytokine structural domain which are covalently linked to form a single polypeptide chain or polypeptide compound. The first binding domain is specifically bound with a tumor associated antigen, and the target spot of the first binding domain comprises but is not limited to KK-LC-1, MSLN, HER2, Claudin18.2, Claudin6 and PSMA; the second binding domain is specifically bound with a CD3 protein complex on the surface of the T cell; the cytokine domain is IL2, IL15, IL12, IL21 or a functional variant thereof. The invention also relates to a nucleic acid molecule for coding the fusion protein, an expression vector and application thereof. The fusion protein can be used for immunotherapy of malignant tumors such as colon cancer, gastric cancer, breast cancer, liver cancer, lung cancer and cervical cancer, and has a good application prospect. The invention effectively solves the problems of insufficient T cell activation and limited killing in solid tumor immunotherapy in the prior art.

The invention provides an application of combination of SPRC and a PD-1 or PD-L1 inhibitor in preparation of a lung cancer immunotherapy sensitizing drug, and relates to the technical field of biomedicine.In the application, through in-vitro cell experiments, cell co-culture experiments and in-vivo animal experiments, S-propargyl-L-cysteine (SPRC) can play a sensitizing role in the anti-lung cancer curative effect of the PD-1 inhibitor, and can be used for preparing a sensitizing drug for lung cancer immunotherapy. The core mechanism is as follows: 30 [mu] M SPRC is in a non-cytotoxic dose window and can specifically inhibit IFN-gamma induced STAT1 phosphorylation and PD-L1 up-regulation by depending on a CSE / H2S pathway, while IFN-gamma-STAT1-PD-L1 is a core signal axis of PD-L1 adaptive up-regulation in lung cancer cells, and the induction effect of TNF-alpha on PD-L1 is relatively weak; meanwhile, SPRC can inhibit activation of NF-kB induced by TNF-alpha and expression of inflammatory factors such as IL-6 and IL-8 through the pathway so as to exert the anti-inflammatory effect, the CD8 + T cell depletion proportion can be remarkably reduced by combining SPRC with anti-PD-1, the synergistic tumor inhibition effect is formed, the effect is verified in in-vivo and in-vitro experiments, and a closed loop of an in-vitro mechanism and an in-vivo curative effect is achieved.

The application discloses a kind of nanobody specifically targeting human and murine NKG2D protein and its preparation method and application.The nanobody or antigen-binding fragment thereof of the application has three complementarity determining regions CDR1, CDR2 and CDR3;Wherein the amino acid sequences of CDR1, CDR2, CDR3 are as shown in SEQ ID NO.2, SEQ ID NO.3, SEQ ID NO.4 respectively.The nanobody can simultaneously bind hNKG2D and mNKG2D with high affinity, and the bispecific nanobody E5 / 2-B12 based on the nanobody can specifically bind CEACAM5 positive tumor cells and NKG2D overexpression cells, and effectively activate NK cells, which can significantly inhibit tumor growth and prolong survival in various tumor models, and has good application prospect in tumor immunotherapy.

The present disclosure provides recombinantly manufactured fusion proteins comprising a HERV-K (HML-2) Env protein fragment or an analog thereof linked to a human Fc fragment. Embodiments include the administration of the fusion proteins to patients having a disease or a disorder with the intention of mitigating and / or reducing the duration of symptoms associated with the condition or disease (for example but not limited to muscular weakness, paralysis and respiratory failure), and / or preventing symptoms associated with the condition or disease, for example, by preventing motor neuron degeneration and cell death in ALS patients associated with the condition or disease. Accordingly, “treatment” generally means both therapeutic treatment and prophylactic or preventative measures. Improvement after treatment may be manifested as a decrease or elimination of such symptoms, e.g., by a decrease or elimination of symptoms associated with ALS, and / or by a decrease in the duration of such symptoms.

The present invention relates to an in vitro method for predicting the response to immunotherapy treatment of hepatocellular carcinoma in a subject, comprising the following steps: 1) A step of determining the energy metabolic state of a liver tissue sample from a subject, wherein the sample comprises pathological tissue and optionally non-pathological tissue, 2) A step of detecting the presence or absence of energy conversion resulting from a reduction in mitochondrial respiration in the pathological tissue by comparing it with a liver tissue sample of the subject or a non-pathological tissue from a standard non-pathological liver sample, Here: - If mitochondrial respiration is reduced in pathological tissue, the subject is less likely to respond to immunotherapy treatment, and - If mitochondrial respiration is not reduced in the pathological tissue, the subject is highly likely to respond to immunotherapy treatment.

The invention relates to an application of a DNAJB4 gene and an encoding protein thereof in preparation of a product for enhancing cancer radiotherapy sensitivity. The DNAJB4 gene provided by the invention is closely related to cancer radiotherapy sensitivity, and overexpression of the DNAJB4 gene is positively related to radiotherapy sensitivity of head and neck squamous cell carcinoma, cervical cancer or breast cancer. A product prepared from the target DNAJB4 selectively degrades DNA-PKcs through a CMA way, high specificity is achieved, and toxicity to normal tissue can be reduced; the radiotherapy remission rate of a patient with high DNAJB4 expression is obviously improved (clinical queue data); the combined treatment prolongs the median lifetime of the mouse model; the drug resistance risk can be reduced by combining with existing therapies (radiotherapy and immunotherapy).

The application belongs to the technical field of nanomedicine, tumor treatment and immunotherapy, and specifically provides a copper death selective induction nanoparticle targeting tumor mitochondria, which is prepared by the following preparation method: S1, TPY is specifically coupled with MHI through a condensation reaction to obtain MTPY; S2, MTPY is complexed with copper ions to obtain an MTPY-Cu complex; and S3, the MTPY-Cu complex is self-assembled with albumin to form an MTPY-Cu@Alb nanoparticle. The copper dose of the application is only 1 / 1000 of that of free Cu 2+ , and the equivalent immune regulation and killing effects can be achieved; the primary tumor and distant tumor foci can be inhibited, and lung metastasis can be reduced; and the application can induce immune memory and prevent recurrence; the application is combined with cisplatin to significantly enhance the therapeutic effect and reverse the induced immunosuppression; and the application has high biological safety, and has no obvious hepatorenal toxicity or hemolytic reaction.

The invention belongs to the field of pathologies affecting the central nervous system: in particular, severe cerebral pathologies, more particularly those restricted by the presence of the blood-brain barrier (BBB): gliomas, cerebral metastases, neurodegenerative diseases (e.g. Alzheimer's, Parkinson's or ALS), genetic diseases (Huntington's, myopathies, Leigh syndrome, Rett syndrome), but also to the field of cancers, musculoskeletal and immunological disorders, vascular diseases (thrombus) in numerous organs (e.g. liver, kidney or muscle) and in combination with numerous therapeutic approaches (e.g. chemotherapy, immunotherapy, targeted therapy or gene therapy). The invention relates to a microbubble comprising a fluorinated polymer or copolymer and a fluorinated gas, to the use thereof and also to the polymer or copolymer intermediate compounds.

The present invention pertains to specific bioparticules at the surface of which are expressed multimeric protein. The bioparticles according to the present invention comprise an envelope consisting of a plasma membrane; and at least one type I or II transmembrane fusion protein anchored in said membrane, said fusion protein comprising successively a) a first monomer of a multimeric protein of interest, b) a coiled-coil domain or oligomerization sequence; and c) a domain for anchoring in the plasma membrane, consisting of a transmembrane segment and a cytosolic segment. Fragments a) and b) are exposed at the surface of the bioparticle, and fragment a) is bound to a second monomer of said multimeric protein by means of a bond which is not a peptide bond. The bioparticles according to the present invention can be used in therapy such as immunotherapy. The present invention also pertains to methods for producing such bioparticles.

The invention discloses an STING agonist polypeptide conjugate as well as a composition and application thereof, and belongs to the field of medicinal chemistry, an STING agonist and a straight-chain peptide or a cyclic peptide are directly connected or connected through a linking group, the formed conjugate can target a tumor microenvironment, and the STING agonist is controllably released in specific time and space, so that the tumor microenvironment is inhibited, and the tumor microenvironment is inhibited. Therefore, the drug enrichment amount of the tumor site is increased, the drug treatment efficiency and bioavailability are improved, the toxic and side effects are reduced, and the purposes of effect enhancement and toxicity reduction are achieved. According to the STING agonist polypeptide conjugate, the targeting property of STING agonist drugs on tumor tissues is improved, the toxic and side effects on normal tissues are reduced, the STING agonist polypeptide conjugate is a brand-new immune agonist type coupling drug, and a new scheme is provided for tumor immunotherapy research.

Systems and methods for destroying or inhibiting cancer cells and other rapidly-dividing cells including an alternating polarity (AP) magnetic field generator and one or more AP electromagnetic coil adapted to be coupled to at least a portion of a patient's body, and a controller to control the AP magnetic field generator and at least one AP electromagnetic coil and cause the field generator and coil to apply AP magnetic field having a frequency of 0.5-500 KHz and a field strength of 0.5-5 mT to the at least a portion of the patient's body area to achieve a desired inhibiting effect on cancer cells or other rapidly-dividing cells. Treatments provided by the system may be co-administered with an anti-cancer therapy such as a chemotherapy drug, a hormone therapy drug, targeted therapy drugs, immunotherapy drugs, an angiogenesis inhibitor drug, or tumor treatment field therapy.