24 results about "Tumour immunotherapy" patented technology

The invention discloses an effect of an Intestinia butyriproducens bacterium in anti-tumor immunotherapy, and finds that colonization of the Intestinia butyriproducens bacterium in intestinal tracts can inhibit growth of CT26 mouse subcutaneous transplanted tumors with poor response to the tumor immunotherapy, meanwhile, growth of human colorectal cancer cells is remarkably inhibited, and apoptosis of tumor cells is promoted for the first time. The application of the Intestinia butyriproducens bacterium in the anti-tumor immunotherapy has the advantages that the effect of the intestinia butyriproducens bacterium in the anti-tumor immunotherapy is achieved, and the application of the intestinia butyriproducens bacterium in the anti-tumor immunotherapy in the anti-tumor immunotherapy in the anti-tumor immunotherapy in the anti-tumor immunotherapy is achieved. Meanwhile, after colonization of the strain and combined administration of PD-1 monoclonal antibodies, the proportion of CD8 + T cells in mouse tumor infiltration lymphocytes is increased, the proportion of depleted PD-1 + CD8 + T cells is reduced, and the proportion of CD8 + T cells releasing functional cell factors interferon gamma and granzyme B is also increased, which shows that after colonization of the strain, the curative effect of tumor immunotherapy can be enhanced, and the tumor immunotherapy effect can be enhanced. The immunoregulation capability and the great clinical application value are realized.

The present invention discloses biphenyloxadiazole ether derivatives as immune checkpoint inhibitors capable of blocking the PD-1 / PD-L1 signaling pathway, as well as their preparation methods and uses. These compounds, as shown in Formula I below, can modulate the PD-1 / PD-L1 signaling pathway to treat a variety of related tumor diseases through tumor immunotherapy, demonstrating potential drug development. The biphenyloxadiazole ether derivatives of the present invention, or their pharmaceutically acceptable salts, racemates, optical isomers, or solvates, are also disclosed. #imgabs0#

The application relates to the technical field of tumor drugs, in particular to application of METTL5 as a tumor immunotherapy targeting site. The base sequence of the METTL5 is shown in SEQ ID No. 1; wherein the METTL5 is a brand-new RNAm6A methyltransferase, is closely related to ribosome translation function, and can regulate the translation of a tumor immune key regulator IL-27; therefore, the METTL5 is used as the tumor immunotherapy targeting site, the expression of the METTL5 related genes or coding proteins is inhibited through targeting, the body anti-tumor immunity can be effectively stimulated, the METTL5 becomes the targeting site capable of enhancing the response rate of tumor immunotherapy, and the METTL5 used as the tumor treatment target point has a wide application prospect in the anti-tumor immunotherapy.

Provided herein are methods, compositions, and kits for treating tumors by combining patient-derived immune effector cells with cytokine and therapeutic agents. In one aspect, apheresis material is processed to isolate at least two products selected from T cell, NK cell, and dendritic cell populations, which are formulated and administered to the patient. In another aspect, invariant natural killer T (iNKT) cells are expanded ex vivo using an IL-15:IL-15Rα complex and α-galactosylceramide delivered on a bacterial minicell nanoparticle, enabling scalable production of functional cells. Additional embodiments include tumor microenvironment preconditioning regimens and use of IL-15 superagonists to convert "cold" tumors into "hot" tumors.

The application belongs to the technical field of drug delivery carrier, and particularly relates to a dual-metal nanodot-oncolytic virus intravenous delivery system and a preparation method and application thereof in tumor immunotherapy. The oncolytic adenovirus is used as raw material, and the dual-metal nanodot-adenovirus chimera is constructed by using the covalent force of 4-maleimide butyric acid-N-succinimidyl ester. The preparation performance, cytotoxicity, action mechanism, in-vivo anti-tumor effect, anti-tumor immunity, anti-tumor recurrence and anti-tumor metastasis effect of the chimera are evaluated. The preparation process is simple, the prepared dual-metal nanodot-adenovirus chimera has small and uniform particle size, is conducive to enrichment in tumor tissues through the enhanced permeability and retention (EPR) effect, has high drug loading capacity, good safety and can generate high-intensity MRI signals at the tumor site. The designed dual-metal nanodot-adenovirus chimera realizes the integration of tumor diagnosis and treatment.

The present invention provides compositions comprising an anti-CD7 chimeric activating receptor (CAR) and an anti-CD7 protein expression blocker, and methods of using such compositions in the treatment of cancer.

The invention discloses a combined treatment strategy of in-vivo in-situ CAR (Chimeric Antigen Receptor) immunotherapy and a cancer vaccine based on circular RNA (Ribonucleic Acid), which is the first novel tumor immunotherapy which combines an in-vivo in-situ CAR-T / M technology based on circular RNA and a circular RNA cancer vaccine technology, and the technology can be used for rapidly and efficiently generating CAR-T / M cells in vivo; and under the clamping action of a corresponding circular RNA cancer vaccine, a synergistically enhanced anti-tumor immunotherapy effect is further generated. Besides, the specific non-complementary region of the I-type intron from tetrahymena is split, and the in-vitro efficient cyclization of RNA can be realized through the self-splicing of the I-type intron under the conditions of no homologous arm and no additional GTP catalysis.

Disclosed in the present invention are a divalent inorganic metal ion / photosensitizer protein nanoparticle, and a preparation therefor and the use thereof. In the present invention, a new technical train of thought is utilized to effectively solve the present defect whereby the immunotherapy effect can only be exerted when a delivered high-valence inorganic oxide is reduced to a divalent state in cells. The nanoparticle is successfully prepared at room temperature in a water solution with a certain pH, and the divalent inorganic metal ion and the photosensitizer entrapped in the nanoparticle form a complex. The nanoparticle has the advantages of stable metal-ion valence and small size, can penetrate deep into tumor tissue via a blood vessel wall, releases the divalent inorganic metal ion after being quickly dissociated in the subacid environment of a lysosome, and plays a phototherapy role. The nanoparticle can damage a lysosome membrane, and breaks through a lysosome barrier to directly transfer Mn2+ to cytoplasm, so that after illumination, the release of double-stranded DNA is induced, cGAMP is generated in-situ in the cytoplasm, a STING signal pathway is activated, the immune response rate is improved, and the treatment effect of the tumor immunotherapy is enhanced. Experiments verify that tumor growth can be completely suppressed in a mouse in-situ breast cancer model.

The present application relates to chimeric receptors, in particular chimeric receptors comprising homodimeric polypeptides. Uses of these receptors in tumor immunotherapy adoptive cell therapy) are also disclosed. The application further relates to methods of genetically modifying a therapeutic immune cell, eliciting an enhanced immune response against a target antigen. The application further relates to therapeutic cells expressing the chimeric receptors and methods of treating patients using the modified therapeutic cells.

The present application relates to the use of hydroxyphenyl propionate compounds of formula (I), (II), (III), (IV) or (V) or pharmaceutically acceptable salts, solvates and / or ester prodrugs thereof for increasing anti-tumor immunity, to compositions comprising them, and to their use, for example, in cancer immunotherapy. More specifically, the present application relates to compounds useful in the treatment of diseases, disorders or conditions that can be treated by increasing the anti-tumor immunity of cells, such as cancer.

The invention belongs to the technical field of biotechnology and cell culture, and particularly relates to an additive for improving killing activity of NK cells, a culture medium and application of the additive and the culture medium. The additive for improving the killing activity of the NK cells comprises an inducer and an amplification agent, the inducer is prepared from auricularia auricula polysaccharide, IL-2, IL-15 and IL-18; the amplification agent is prepared from timosaponin, isoalantolactone, tannic acid and IL-2 (Interleukin-2). By adding the black fungus polysaccharide auxiliary cytokines, the NK cells can be effectively activated in the induction period, and the expansion efficiency of the NK cells is promoted to be improved; according to the NK cell proliferation culture medium, the NK cell proliferation culture medium is added with the isoalantolactone, the tannic acid and the cell factors for synergistic cooperation in the proliferation period, the proportion of CD3-CD56 + cells can be effectively increased on the basis of achieving NK cell proliferation culture, the immunocompetence of the NK cells and the killing effect of tumor cells are enhanced, and application of the NK cells in tumor immunotherapy is promoted.

Provided is an in-vivo in-situ CAR immunotherapy and cancer vaccine combined therapy strategy based on circular RNA, which is a novel tumor immunotherapy that combines the cyclic RNA-based in-vivo in-situ CAR-T / M technology and the circular RNA cancer vaccine technology. This novel tumor immunotherapy enables rapid and efficient generation of CAR-T / M cells in vivo and further produces an enhanced collaborative anti-tumor immunotherapy effect with the synergistic action of the corresponding circular RNA cancer vaccine. In addition, a specific non-complementary region of an I-type intron from tetrahymena is split, and thus in-vitro efficient RNA cyclization can be achieved by means of self-splicing of the I-type intron without requiring homologous arms or additional GTP catalysis.

Provided are compositions and methods for treating cancer using administration of certain volumes of CpG oligonucleotides (CpG ODN) and, optionally, administration of a checkpoint inhibitor such as an anti-PD-1 antibody, an anti-PD-L1 antibody, and / or an anti-CTLA-4 antibody. In preferred embodiments, the CpG ODN are selected based on their propensity to induce high amounts of interferon alpha (IFN-a) and T-cell activation relative to interleukin-10 (IL-10) and B-cell activation. In certain embodiments, the methods further include pretreatment with radiotherapy, to potentiate the combination immunotherapy.

The invention relates to the technical field of tumor immunotherapy, and particularly discloses a screening method of a cancer cell mitochondrial DNA (deoxyribonucleic acid) coding new antigen, mitochondrial DNA with higher purity is obtained by means of microdissection, linear DNA splitting and the like, and nuclear metastasis mitochondrial fragment interference in mitochondrial sequencing is overcome. On the basis, mitochondrial amplicon sequencing is used for identifying the base sequence change caused by mutation from the DNA level, multiple types of tumor vaccines including polypeptide vaccines, RNA vaccines and dendritic vaccines can be prepared according to requirements, and even the tumor vaccines can be used for TCR-T therapy. According to the screening method of the mitochondrial DNA coding new antigen and the application of the mitochondrial DNA coding new antigen in preparation of the vaccine, the feasibility of the mitochondrial coding new antigen and the effectiveness of the mitochondrial coding new antigen as a tumor vaccine target are accurately and comprehensively confirmed, and a transcription translation process and a screening mechanism of DNA-RNA-polypeptide are systematically constructed; and more diversified, personalized, safe and effective treatment strategies can be selected and designed for the patient.

The present disclosure provides compositions and methods for inhibiting T cell senescence and improving T cell immunotherapies. In particular, inhibitors of group IV A phospholipase A2 are disclosed as useful in modulating the lipid metabolism of cells, in particular effector T cells, such that T reg- and tumor cell-induced cell senescence is abrogated. These methods may be employed with particular utility in adoptive T cell therapies and / or enhanced T cell effector functions in vivo, including those performed in combination with checkpoint blockade therapies.

The present invention discloses an anti-CD40 antibody, an anti-PD-L1×CD40 bispecific antibody, and their uses. The anti-CD40 antibody includes a heavy chain variable region and a light chain variable region. The heavy chain variable region includes HCDR1, HCDR2, and HCDR3 of SEQ ID NO: 64, and the light chain variable region includes LCDR1, LCDR2, and LCDR3 of SEQ ID NO: 65. The novel anti-CD40 agonist antibody of the present invention can effectively regulate the activation of DC cells, has a stronger T cell activation effect, has low toxicity and side effects, and is suitable for tumor immunotherapy. The bispecific antibody of the present invention can maximize the antitumor effect, improve the selectivity of CD40 activation through PD-L1-dependent CD40 activation, and reduce the toxicity and side effects of the CD40 agonist antibody.

Provided are a polypeptide targeting a KRAS mutant protein and a use thereof, a drug, and a method. The polypeptide can specifically bind to a KRAS G12 mutant protein binding domain, can exhibit high affinity to a KRAS G12X mutant protein (X=D, V, R, or C), with a picomolar-level equilibrium dissociation constant KD, and can specifically regulate and control a secondary structure of the KRAS G12X mutant protein (X=D, V, R, or C). The polypeptide conforming to specific amino acid composition and sequence characteristics and including SEQ ID NOs. 1-9 has the ability to induce death of KRAS G12X mutant (X=D, V, R, or C) tumor cells and, on this basis, enhances the therapeutic effect of existing chemotherapy and tumor immunotherapy. The polypeptide can be used as a therapeutic or auxiliary therapeutic drug for diseases, such as colon cancer, lung cancer, pancreatic cancer, breast cancer, osteogenic sarcoma and / or ovarian cancer, and has clinical application potential.

Provided is a polypeptide combination, a targeting component thereof comprising a shielding peptide, a cleavable part, an antigen-binding part and a first intein fragment, the shielding peptide and the antigen-binding part being connected by means of the cleavable part, and the antigen-binding part being directly or indirectly connected to the first intein fragment; a toxin component thereof comprises a second intein fragment and a toxin, and the second intein fragment is directly or indirectly connected to the toxin; the targeting component and the toxin component form an immunoconjugate by means of the interactive action between the first intein fragment and the second intein fragment; in the immunoconjugate, the shielding peptide and the antigen-binding part are connected by means of the cleavable part, and the antigen-binding part is connected to the toxin. Also provided are a preparation method and a pharmaceutical use for the polypeptide combination.

The present disclosure provides a chimeric antigen receptor (CAR) immunotherapy for treating a hematologic cancer comprising (a) genetically modifying a population of immune effector cells comprising T cell receptors (TCRs) to stably express at least one CAR, wherein the ectodomain of the CAR specifically binds a cancer antigen; (b) expanding the population of CAR-containing immune effector cells in the presence of one or more cytokines in vitro to achieve a therapeutic dose, wherein the population of CAR-containing immune effector cells exhibits a nonexhausted memory T cell phenotype; and (c) infusing eligible subjects with the CAR-containing immune effector memory T cell phenotype population of cells as needed until the hematologic cancer in the body is destroyed. The intracellular signal transduction domain of the CAR includes 4-1BB, a CD3zeta T cell activation chain and a genetically engineered 'TLE3, which can be ectopically expressed.

The present invention provides chimeric cytokine receptors, particularly chimeric cytokine receptors that can be activated in tumor microenvironment, and their uses in tumor immunotherapy (e.g., adoptive cell therapy). The present invention further provides methods of genetically modifying therapeutic cells resulting in an enhanced immune response against a target antigen. The application further provides therapeutic cells that express said chimeric cytokine receptors and methods for treating patients using the modified therapeutic cells.

The application relates to chimeric cytokine receptors, particularly chimeric cytokine receptors comprising one or more leucine zipper motifs, and their uses in tumor immunotherapy (e.g., adoptive cell therapy). The application further relates to methods of genetically modifying therapeutic immune cells resulting in an enhanced immune response against a target antigen. The application further relates to therapeutic cells that express said chimeric cytokine receptors and methods for treating patients using the modified therapeutic cells.

This invention belongs to the field of biomedical technology and relates to protein polyphenol nanocapsules, their preparation method, and their application in the preparation of nanovaccines. Eight-arm polyethylene glycol-hydroxyl groups, IMDQ, 2-MIM, and zinc salt are used in water as a solvent to prepare IMDQ-loaded ZIF-8 nanoparticles. The IMDQ-loaded ZIF-8 nanoparticles are dispersed in water, and OVA is added for mixing and reaction, allowing the IMDQ-loaded ZIF-8 nanoparticles to adsorb OVA. The OVA-adsorbed IMDQ-loaded ZIF-8 nanoparticles are then dispersed in water, and tannic acid is added for reaction, causing the tannic acid to etch ZIF-8 to form a hollow structure. This hollow structure serves as a framework for the interaction between tannic acid and OVA to form protein polyphenol nanocapsules. The protein polyphenol nanocapsules prepared by this invention exhibit good biocompatibility and immunogenicity and can be used as nanovaccines for tumor immunotherapy.

The application provides chimeric antigen receptors (CARs) that target leucine rich repeat containing 15 (LRRC15), and their uses in tumor immunotherapy. The application also provides polynucleotides and vectors that encode the CARs, as well as host cells comprising the CARs. The application also provides methods for preparing host cells comprising the CARs and methods for treating patients using the modified host cells.

The present invention relates to a humanized anti-human OX40 monoclonal antibody, and a preparation method and use thereof. The humanized anti-human OX40 monoclonal antibody provided in the present invention has high affinity and specificity for OX40, and can stimulate T cells to secrete cytokines, for example, specifically activate the positive immune regulation by OX40 and activate T cells to secrete cytokines. Therefore, the functional humanized anti-human OX40 monoclonal antibody provided in the present invention activates T cells by activating the OX40 signaling pathway, thereby achieving the purpose of tumor immunotherapy.