59 results about "Tumor immunosuppression" patented technology

The present invention relates to novel 39-desmethoxy-39-methylrapamycin derivatives, methods for their production, and uses thereof. In a further aspect the present invention provides for the use of these 39-desmethoxy-39 -methylrapamycin derivatives in the treatment of cancer and / or B-cell malignancies, the induction or maintenance of immunosuppression, the treatment of transplantation rejection, graft vs. host disease, autoimmune disorders, diseases of inflammation, vascular disease and fibrotic diseases, the stimulation of neuronal regeneration or the treatment of fungal infections.

The present invention relates to the application of the diterpene lactone compound (HQ-091212) represented by formula (1) in the preparation of antitumor drugs and immunosuppressants. The pharmaceutical composition of the present invention can be made into tissues and organs beneficial to mammals The dosage form for absorption and utilization has good application prospects in the treatment of proliferative diseases such as tumors and immunosuppression.

The invention provides an aspirin derivative. The aspirin derivative has a structure as shown in a formula (I) which is described in the specification. The aspirin prodrug with the structure has the capability of sensitively releasing aspirin or salicylic acid under the stimulation of active oxygen or ultraviolet light; furthermore, the sensitive aspirin prodrug with the structure is combined to aspecific polymer carrier; an obtained bonding drug can be enriched to tumor tissues and rapidly release the drug, so that the bonding drug has a wide development prospect in the fields of reducing inflammation of the tumor tissues, improving a tumor immunosuppression microenvironment and inhibiting tumor growth. The aspirin polymer prodrug provided by the invention can be enriched at a tumor or inflammatory site, improve the in-vivo metabolic pathway of aspirin, and can effectively solve the problems of short action time and poor curative effect of micromolecular aspirin. Moreover, the preparation method provided by the invention is simple, wide in raw material source and capable of realizing batch production and industrialization.

The invention relates to calcium carbonate based compound micro particles and preparation and application thereof. The calcium carbonate based compound micro particles disclosed by the invention comprise calcium carbonate and a macromolecule stable layer, wherein the macromolecule stable layer comprises amphipathic molecules and / or hydrophilic molecules. The invention further discloses applicationof the calcium carbonate based compound micro particles to preparation of one or more of an adjuvant, a chemotherapy enhancing adjuvant, a radiotherapy enhancing adjuvant and a radiofrequency ablation treatment adjuvant for tumor immnuotherapy. The calcium carbonate based compound micro particles disclosed by the invention have an excellent effect of regulating a tumor slight acid environment, can reduce content of immunosuppressive cells in tumor, increase content of immune cells capable of killing the tumor and promote polarization of tumor-associated macrophages from the M2 type to the M1type, effectively turns the tumor immunosuppression micro environment, activate antitumor immunity, and can enhance a suppression effect of various treatment means of immunotherapy, chemotherapy, radiotherapy, radiofrequency ablation treatment and the like on tumor growth.

The invention provides a biomarker analysis method based on multiple immunohistochemical technologies and application thereof. According to the biomarker analysis method, histomorphology, cell phenotype and corresponding space coordinate information of a tumor tissue sample of an image recognition system are utilized, and the tumor immune microenvironment is automatically analyzed through two biomarkers including double-positive cell scoring and tumor-immunosuppression relative distance ratio. The invention also provides a device and equipment for implementing the method, and a corresponding computer readable medium. By means of the method, the space connection state of the tumor immune microenvironment can be more accurately and efficiently represented, the tumor immune microenvironment related indexes can more effectively evaluate the immune treatment effect, and the requirements for tumor immune microenvironment analysis through multiple immunohistochemical technologies in clinical pathological work and scientific research are met.

The present invention relates to a calcium carbonate poly(lactic acid-glycolic acid) composite particle and a preparation and an application thereof. The calcium carbonate poly(lactic acid-glycolic acid) composite particle is prepared by using alkyl-modified NLG919, polylactic acid-glycolic acid and polylactic acid-glycolic acid-polyethylene glycol as a shell layer, and calcium carbonate and doxorubicin as a core layer. The present invention also discloses the application of the calcium carbonate poly(lactic acid-glycolic acid) composite particle in preparation of drugs for tumor chemotherapyor combined tumor chemotherapy and immune therapy. The composite particle can be used as a drug carrier, has good drug loading efficiency and tumor enrichment ability, realizes co-loading of a chemotherapy drug DOX and an IDO inhibitor aNLG919, can also effectively release the chemotherapy drug doxorubicin and also inhibit IDO immunosuppressive pathways, effectively reverses tumor immunosuppressive microenvironment, activates tumor immunity, inhibits tumor growth, and realizes tumor chemotherapy or combined chemotherapy and immune therapy.

The present invention discloses an antibody with double MIC binding activity and application thereof. The antibody comprises at least one heavy chain variable region comprising three CDRs and at least one light chain variable region comprising three CDRs, the light chain variable region and the heavy chain variable region thereof The CDR sequence of the chain variable region is described in SEQ ID NO.1-30. The anti-MIC antibody of the present invention has a good affinity effect on various MICA and MICB proteins, especially has binding activity on soluble MICA*008, MICA*010, MICA*002, MICA*009 and MICB*005, through Adsorption of NKG2D ligands in human blood or plasma, including soluble MICA, MICB molecules and immune complexes composed of MICA / B and anti-MIC monoclonal antibody drugs, can relieve the tumor immunosuppressive effect caused by the abnormal increase of MIC protein.

The present invention relates to the field of tumor cell immunotherapy, and in particular to a recombinant lentivirus and its application. The recombinant lentivirus contains a chimeric antigen receptor, and the chimeric antigen receptor mainly includes a signal peptide, an antigen recognition region, a transgenic A membrane region, an intracellular co-stimulatory signal transduction domain and a CD3ζ signal transduction domain are formed in series; wherein, the intracellular co-stimulatory signal transduction domain mainly includes the intracellular region of human TLR2. The GPC3 CAT T cells prepared by the present invention have a strong cell killing effect on liver cancer cells, and highly express Th1 cytokines, which can greatly stimulate the tumor killing effect caused by non-CAR T cells, and can effectively prevent the escape and potential of GPC3 tumor cells. The threat of recurrence, and T cells expressing this chimeric antigen receptor can kill tumor cells to the greatest extent, with little damage to normal tissues, and can break through the tumor immunosuppressive microenvironment, thus having better curative effect on solid tumors.

The invention discloses an application of a TMUB1 protein in preparation of a tumor immunosuppressive molecule detection agent, and provides a method for detecting the expression level of the TMUB1 protein and an application of a TMUB1 protein inhibitor in inhibition of tumor immunosuppressive molecules at the same time, in the invention, the TMUB1 with low expression level can significantly reduce the protein level of PD-L1, PD-L1 protein accumulation in tumor cells is blocked from the root of PD-L1 protein synthesis, and immune escape of the tumor cells is blocked.

Provided are a chimeric immune inhibitory checkpoint receptor molecule, a nucleic acid encoding the same, a construct, expression vector and transformed cell containing the nucleic acid, and a pharmaceutical use thereof. The chimeric immune inhibitory checkpoint receptor molecule comprises an extracellular domain, a transmembrane domain, and an intracellular domain. The extracellular domain and the optional transmembrane domain are corresponding domains of an immune inhibitory checkpoint receptor molecule or are genetically engineered on the basis of the corresponding domains. The intracellular domain is one or more immune activation signal domains. The transformed cell has a strong tumor-killing effect and can abrogate a tumor-immunosuppressive microenvironment, thereby strengthening an immune response in the tumor microenvironment. The transformed cell also has a self-regulation function and can alleviate side effects such as an overactive, non-specific immune response and a cytokinestorm.

The invention relates to a single chimeric converter for a T-cell signal and application thereof, which belongs to the fields of molecular biology and immunology. Specifically speaking, the single chimeric converter is formed by connection of a polypeptide highly efficiently bonding with immunosuppression molecules on the surfaces of tumor cells and / or tumor matrix cells to a transmembrane domain originated from a high-affinity receptor and an intracellular peptide fragment of a costimulatory signal molecule through a hinge structure. Out-membrane polypeptide receives a signal of the immunosuppression molecules on the surfaces of tumor cells and / or tumor matrix cells and transmits the signal into a cell, a second signal of immune cells is activated through the intracellular peptide fragment of the costimulatory signal molecule, so multiplication capacity of the immune cells and the secretion function of cell factors are enhanced, and the survival time of the activated immune cells is prolonged; thus, side-effects of a tumor immunosuppression microenvironment on adoptive cell therapy effector cells are overcome.