274 results about "T lymphocyte" patented technology

The present invention relates to T lymphocytes targeting CLD18A2 and a preparation method and application thereof. The inventors have successfully found a target gene CLD18A2 suitable for developing CAR T cells from a number of tumor-related genes for the first time, and successfully prepared CAR T cells targeting CLD18A2, thereby providing a new treatment method for pancreatic cancer, gastric cancer and other tumors.

The invention belongs to the technical field of inspection and extraction, and particularly relates to an automatic T lymphocyte suction device which comprises an automatic suction device body, the automatic suction device body comprises a bearing table, a rotating disc with a circumferential rotating function is arranged on the bearing table, and a plurality of centrifugal assemblies are evenly distributed on the rotating disc. A centrifugal tube feeding assembly facilitating feeding of centrifugal tubes is arranged in front of one side of the bearing table, a tube carrying and conveying assembly is arranged on the portion, located on one side of the centrifugal tube feeding assembly, of the bearing table, a tube feeding mechanism is arranged at the end of the conveying belt mechanism, and a reaction reagent adding assembly is arranged on one side of the tube carrying and conveying assembly. A sample feeding assembly is arranged on one side of the upper portion of the workbench, and a first suction assembly is arranged above the multi-direction adjusting assembly. According to the invention, multiple samples can be processed in batches, the working efficiency and the cell extraction purity are improved, the influence of manual operation on the result is reduced, the accuracy of the detection effect is ensured, and the use requirements are met.

The invention relates to the field of tumor cell therapy, in particular to application of T lymphocyte chimeric with a B7-H3 receptor to treatment of head and neck tumors, and provides an anti-B7-H3 scFv, the scFv comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises an HCDR region and an HFR region, and the light chain variable region comprises an LCDR region and an LFR region; compared with a wild type scFv sequence, the scFv sequence has the advantage that a plurality of amino acids with positive charges in the HFR region and / or the LFR region are mutated into amino acids without charges. According to the invention, positive charge plaques on the CAR surface of an scFv sequence of a B7-H3 human-derived monoclonal antibody MGA271 are changed in a charged amino acid mutation manner, so that a B7-H3. CAR-T cell is optimized, and it is proved that the B7-H3. CAR-T cell optimized by PCP can effectively kill B7-H3 positive tumor cells in vivo and in vitro; and a new method and thought are provided for clinical targeted treatment of B7-H3 positive solid tumors.

The invention belongs to the field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating triple negative breast cancer and application thereof. The traditional Chinese medicine composition is prepared from the following main active ingredients in parts by mass: 20 to 40 parts of radix astragali seu hedysari, 10 to 20 parts of rhizoma curcumae, 10 to 20 parts of herba hedyotidis diffusae, 5 to 15 parts of fructus aurantii immaturus, 5 to 15 parts of radix bupleuri, 5 to 15 parts of radix paeoniae alba and 5 to 15 parts of liquorice root. Animal experiments show that the traditional Chinese medicine composition can significantly inhibit tumor growth and pulmonary metastasis of triple-negative breast cancer tumor-bearing mice, increase the proportion of CD8 + T lymphocytes in blood, reduce the proportion of MDSCs, significantly down-regulate the expression of pro-inflammatory cytokines such as IL-6, IL-1alpha, CXCL1 and GM-CSF in serum, and cooperate with PD-L1 immunotherapy to achieve a synergistic effect. And the whole blood and liver and kidney function indexes are in a normal range. Therefore, the traditional Chinese medicine composition disclosed by the invention can be used for effectively inhibiting the tumor growth and pulmonary metastasis of the triple negative breast cancer, remodeling the immune state of an organism and reducing the release of proinflammatory factors, and is safe, reliable, free of obvious liver and kidney toxicity and blood toxicity and small in side effect.

An antigen peptide is provided specifically for treating individuals suffering from ovarian cancer, preferably based on BRCA1 gene c. 5470_5477del8 mutation. It is selected from amino acid sequences of SEQ ID NO. 1 to SEQ ID NO. 6, or derived by substitution, deletion and / or addition of at least one amino acid. The neoantigen polypeptides of the present disclosure can significantly activate T lymphocytes specific to the BRCA1 gene c. 5470_5477del8 mutation in vitro, stimulating the release of the cytokine IFN-y, indicating notable immunogenicity. This enhances T lymphocytes' ability to target and kill cancer cells from ovarian cancer patients carrying the BRCA1 gene c. 5470_5477del8 mutation. Additionally, the antigen peptide can activate and expand human T lymphocytes specific to the BRCA1 gene c. 5470_5477del8 mutation in vitro for adoptive cell therapy. The antigen peptide of the present disclosure addresses the gap in personalized antigen peptide therapies for ovarian cancer patients with BRCAl-c. 5470_5477del8 somatic mutations.

The invention belongs to the technical field of biological medicines, and particularly discloses a nano-engineering T cell membrane coated nano-particle as well as a preparation method and application of the nano-engineering T cell membrane coated nano-particle. Nanoparticles of a specific structure are constructed based on a phospholipid bilayer bionic nanometer platform through a membrane fusion technology, immune clearance caused by phagocytosis of the nanoparticles by macrophages can be avoided through disguise of a T cell membrane, and the blood circulation time is prolonged; the functions of T cells are recovered through specific blocking of immune checkpoint molecules loaded on the immune checkpoint molecules on corresponding immune checkpoint ligands on tumor cells; under ultrasonic radiation, the nano-particles are gradually decomposed and release the sound-sensitive agent to generate a large amount of active oxygen, so that immunogenic death of tumor cells is promoted, more cytotoxic T lymphocytes are recruited to infiltrate into tumor parts, and the recovery of T cell mediated immune response function is facilitated. The synergistic effect of the sound-sensitive agent and the immune checkpoint protein can effectively inhibit tumor growth, induce a long-term immune memory effect and prevent tumor metastasis and recurrence.

The invention belongs to the technical field of biological medicines, and particularly relates to an antigen peptide library for inducing tumor specific immune response, the antigen peptide library comprises eight antigen peptides, and the amino acid sequences of the eight antigen peptides are respectively shown as SEQ ID NO.1-SEQ ID NO.8. The invention further discloses a preparation method of the antigen peptide library. The antigen peptide has high immunogenicity and can effectively stimulate and induce generation of specific cytotoxic T lymphocytes when being loaded on antigen presenting cells, in-vitro killing experiments show that CTL cells induced and activated by loading new antigen DC have a high tumor killing effect, and the cell killing activity of the CTL cells is 90% or above. When model mice are treated by adoptive T cell back-transfusion of CTL cells induced by the new antigen peptide library, the tumor volume can be effectively reduced, the survival rate of the tumor can be remarkably increased, and good treatment potential is achieved.

The invention provides an application of a spleen T lymphocyte exosome in construction of a depression animal model, a stress rat spleen T lymphocyte exosome is injected into a mouse body to construct the depression animal model, and the depression animal model can be used for depression drug screening, drug efficacy evaluation or diagnosis, and can be used for treating depression. And the method can also be used for researching and revealing pathogenesis of depression. The invention also proves that the IL4 / IL4R alpha signal channel and the BDNF signal channel play an important role in depression through experiments. The invention has important significance for clinical research of depression.

The present invention relates to an immunoprophylactic and therapeutic vaccine comprising a peripheral blood mononuclear cell loaded with a natural killer T cell ligand and an antigen, and more particularly, to an immunotherapeutic vaccine comprising a peripheral blood mononuclear cell loaded with alpha-galactosylceramide, a natural killer T cell ligand and a glycolipid. The compositions of the present invention are readily available because there is no need to isolate specific cells from peripheral blood mononuclear cells. Besides, the immunization of the peripheral blood mononuclear cells loaded with the natural killer T cell ligands and antigens not only induces the obvious-level activation of the natural killer cells and the natural killer T cells and the response of cytotoxic T lymphocytes, but also has a synergistic treatment effect in the aspect of treating malignant tumors. Therefore, the compound can be beneficially used as an anti-cancer immunotherapeutic agent.

The invention relates to the field of biological medicine, in particular to application of fermented lactobacillus mucus in preparation of immune antitumor drugs. A strain of fermented lactobacillus mucus capable of effectively treating tumors is screened and can activate the immune system of the strain, increase the proportion of CD8 + T lymphocytes in spleen tissues, increase the infiltration proportion of leukocytes in tumors and the proportion of CD4 + and CD8 + T lymphocytes in infiltrated immune cells, change the tumor microenvironment and improve the tumor immunity. Therefore, tumor cells are effectively killed, and the effect of tumor immunotherapy is achieved.

An anti-CTLA4 (cytotoxic T lymphocyte associated antigen 4) and anti-PD-1 (programmed cell death 1) bifunctional antibody. a pharmaceutical composition thereof and use thereof. Particularly, the anti-CLTA4 and anti-PD-1 bifunctional antibody comprises a first protein functional domain that targets PD-1 and a second protein functional domain that targets CTLA-4. The bifunctional antibody can bind to CTLA-4 and PD-1 specifically, relieve immunosuppression of CTLA4 and PD-1 on an organism specifically, activate T lymphocytes, and thus has good application prospects.

The invention belongs to the technical field of biological medicine, and particularly discloses nano composite particles based on a metal organic framework and a preparation method and application of the nano composite particles. The nano-composite particles are constructed through electron adsorption and coordination based on a nano-scale metal organic framework, and under the acidic microenvironment and ultrasonic irradiation of tumors, the nano-composite particles can be decomposed and released in a responsive manner, play a role of a sound-sensitive agent, generate a large amount of active oxygen and induce tumor cells to generate immunogenic death, so that the tumor cell immunogenicity is improved, and the tumor cell immunogenicity is improved. Further, more cytotoxic T lymphocytes are promoted to infiltrate a tumor microenvironment, T cell mediated anti-tumor immune response is recovered, and tumor metastasis is effectively prevented. The carrier metal organic framework ZIF8 of the nano-composite particles can serve as a sound-sensitive agent to generate active oxygen, the function of ultrasonic imaging of tumor tissue can be achieved, the effect of diagnosis is achieved while treatment is conducted, tumor diagnosis and treatment monitoring can be achieved at the same time through one-time drug administration, and a new strategy is provided for precise medical treatment.

The invention relates to a prostatic cancer targeting CAR (chimeric antigen receptor), a recombinant expression vector containing the same, a lentivirus, CAR-T and application, and belongs to the technical field of tumor immunotherapy. In order to solve the problem that few reports are reported for treating solid tumors by CAR-T cells, the invention provides a CAR for targeting prostatic cancer, the CAR comprises an scFv fragment consisting of VH with an amino acid sequence as shown in SEQ ID NO.2, a hinge region (Gly4Ser) 3 and VL with an amino acid sequence as shown in SEQ ID NO.4, the CAR is connected to a lentiviral expression vector pLV-EF to obtain an expression vector plasmid, and the expression vector plasmid is used for expressing the prostatic cancer. The CAR-T cell is prepared by producing a high-titer lentivirus through a 293T packaging cell line, human primary T lymphocytes infected and activated by the lentivirus are used for preparing the CAR-T cell, in-vivo and in-vitro experiments prove that the CAR-T cell has a specific killing effect on prostatic cancer, and a new treatment thought and means are provided for solid tumor treatment.

The present invention is related to an alcoholic formulation comprising a mixture of alkaloids, specifically piperine, piperettine, trichostaquine, piperoleins, other alkamides, and / or other alkaloids, as well as terpenoids, phenolics, prenol lipids, and flavonoids. The formulation is particularly rich in piperines, which are found in greater proportion compared to the other compounds. This unique composition exhibits anti-tumor activity in vitro, reducing tumors generated by orthotopic transplantation of tumors in animal models. Furthermore, it modulates the immune response by reducing the frequency of intratumoral immunosuppressive cells and increasing the frequency of cytotoxic T lymphocytes, thereby promoting tumor destruction and controlling metastasis.

The invention discloses a key effect and a targeted intervention strategy of YTHDF1 in regulation and control of a hepatocellular carcinoma immunosuppression microenvironment. In the tumor-associated fibroblasts, YTHDF1 enhances the translation efficiency of OTUD5 mRNA through an m6A dependency mechanism, an up-regulated deubiquitination enzyme OTUD5 is directly combined with a tryptophan metabolic rate-limiting enzyme IDO1, ubiquitination degradation of the tryptophan metabolic rate-limiting enzyme IDO1 is inhibited, tryptophan is further driven to catabolism to generate kynurenine, regulatory T cell differentiation is promoted, and an immunosuppression microenvironment is formed. Spatial transcriptomics shows that YTHDF1 + CAFs and Tregs are significantly co-localized in tumor tissues and have metabolic interaction. Based on artificial intelligence virtual screening, it is found that a natural compound hesperidin can be specifically combined with a YTH structural domain of YTHDF1, an OTUD5-IDO1 signal axis mediated by the natural compound hesperidin is blocked, and the KYN level is remarkably reduced. Animal experiments prove that the tumor inhibition rate of combined treatment of hesperidin and anti-PD-1 is increased by 40% or above compared with that of a single drug group, and synergistic interaction is achieved by inhibiting Tregs infiltration and enhancing the activity of cytotoxic T lymphocytes.

The invention relates to the field and discloses application of terahertz waves or intermediate infrared in preparation of adoptive T lymphocytes. The Terahertz wave or mid-infrared modulation technology is utilized to specifically regulate and control the functions of the T cells in a flowing irradiation mode, and the functions of the T cells from different sources are enhanced under the conditions that no medicine is used and no exogenous gene is introduced. Terahertz wave or mid-infrared stimulation is applied to the T cells in a flowing irradiation mode, specific terahertz wave or mid-infrared frequency for remarkably enhancing the functions of the T cells is determined in a frequency screening mode, and after the optimal irradiation frequency is determined, the T cells with the most remarkable function improvement are further input back into a donor. The T cells stimulated by terahertz waves or mid-infrared rays can play a powerful immune function in a tumor microenvironment so as to inhibit further development of tumors.

Described herein are receptor configurations that allow ligation of multiple targets expressed in cancer cells via two main mechanisms: direct binding via an antibody-derived single chain variable fragment (scFv), and indirect binding through the high-affinity engagement of the Fc component of an antibody. When expressed in human T lymphocytes, these receptors (CARFcR) can trigger powerful CAR-T cell activity as well as antibody- dependent cell cytotoxicity (ADCC), either simultaneously or sequentially. CARFcR T cells are not affected by soluble antibodies, but they can be redirected and activated by antibodies bound to target cells. Therefore, such T cells can be used to redirect adoptive T cell therapy towards another tumor-associated antigen "on the fly" using clinically available antibodies. They also provide a practical way to target multiple antigens simultaneously with a single receptor, a feature that should be useful in cell therapies directed against phenotypically heterogeneous tumors.

The invention discloses application of sea cucumber polysaccharide in the process of assisting anti-PD-1 in treating colon cancer, and belongs to the technical field of medicine. The SCP pretreatment is combined with the anti-PD-1 immunotherapy, so that the curative effect of the anti-PD-1 immunotherapy is remarkably enhanced. Researches show that single use of the SCP has no significant inhibition effect on tumor growth, but the SCP can significantly enhance the anti-tumor effect of anti-PD-1 treatment. The SCP combined with anti-PD-1 treatment can increase the number of CD8 < + > T lymphocytes, especially IFN-gamma < + > cytotoxic CD8 < + > T cells, and reduce the proportion of regulatory CD4 < + > T cells at the same time. The SCP improves the immunotherapy effect by adjusting intestinal flora and increasing the relative abundance of beneficial bacteria such as bifidobacteria and fecal bacillus, and fecal flora transplantation experiments show that the tumor immunotherapy enhancing effect of the SCP is at least partially mediated by the intestinal flora.

The present invention relates to a complex comprising a polysaccharide conjugate, an anti-PD-L1 monoclonal antibody, and a PKM2 inhibitor. The complex of the present invention can accumulate and remain in tumor tissue, effectively stimulate dendritic cell maturation, alleviate the inhibitory immune microenvironment, and trigger a specific anti-tumor immune response. It can effectively inhibit the expression of PKM2, thereby inhibiting glycolysis in tumor tissue and providing a more favorable environment for T lymphocytes to infiltrate tumor tissue. The complex of the present invention is expected to enhance the therapeutic effect of RFA on patients with advanced HCC by reprogramming iRFA-induced tumor immunosuppression, and has great potential in improving the prognosis of patients with advanced HCC treated with RFA.

The invention provides a polypeptide for activating cellular immunity in chronic hepatitis B and application of the polypeptide, and belongs to the technical field of biological medicine. A polypeptide library is designed and synthesized on the basis of a preS1 structural domain for coding HBV large HBsAg, a full-length core protein Core, a polymerase protein fragment rich in T cell epitopes and an mRNA-PreS1CPX holoantigen sequence (as shown in SEQ ID NO.1) of full-length X protein HBX, and peptide fragments capable of activating T cell immunity are screened by utilizing ELISPOT and flow cytometry. Experimental results show that the polypeptide sequences as shown in SEQ ID NO.2-15 can promote HBV antigen specific immune response by stimulating CD8 + T lymphocytes to secrete IFN-gamma, so that immune activation treatment of hepatitis B is realized.

The present invention relates to canine antibodies, binding polypeptides, and scFvs specific for canine cytotoxic T lymphocyte associated protein 4 (CTLA-4).

The application discloses a use of Ejiao Qianggu oral liquid in regulating immunity, and particularly relates to an improving effect of the Ejiao Qianggu oral liquid on an immune system, which is realized by the following aspects. On one hand, the Ejiao Qianggu oral liquid promotes proliferation and transformation (mainly early T lymphocytes and part of B lymphocytes) and active functions of spleen lymphocytes; on the other hand, the Ejiao Qianggu oral liquid improves phagocytosis of macrophages. The Ejiao Qianggu oral liquid has the following characteristics: firstly, the Ejiao Qianggu oral liquid acts on early lymphocyte maturation, and has no significant effect on proliferation of peripheral blood lymphocytes; secondly, the Ejiao Qianggu oral liquid can significantly act on immune target organs, thymus and spleen tissues, and does not excessively stimulate the spleen, unlike positive drugs such as colony stimulating factor which can cause significant edema of the spleen; and thirdly, the Ejiao Qianggu oral liquid has a significant recovery effect on body weight, white blood cells, lymphocytes, red blood cells and hemoglobin in blood of patients with low immunity.

The invention provides modified an isolated T lymphocytes having reduced or eliminated expression of the T Cell Receptor, due to reduced or eliminated expression of a CD3ζ, T Cell Receptor Alpha Chain, or T Cell Receptor Beta Chain gene relative to a T lymphocyte without modification, where the isolated T lymphocyte expresses a protein comprising US6, UL40 viral protein and signal peptide, and UL18.

The present invention relates to immune cells that express immune checkpoint regulators and overcome immune checkpoints, a method for producing the same, and a pharmaceutical composition containing the immune cells. More specifically, the present invention relates to immune cells that are genetically engineered to express an anti-HLA-G soluble scFv that specifically binds to HLA-G, which is an immune checkpoint, together with an antigen recognition receptor, a method for producing the same, and a pharmaceutical composition containing the immune cells. When the anti-HLA-G soluble scFv of the present invention is expressed alone or simultaneously with an antigen recognition receptor in T lymphocytes, natural killer cells, etc., immune cells inhibited by cancer cells expressing immune checkpoints can be activated, and cancer cells can be removed more efficiently. Thereby, activation of endogenous immune cells that have been inhibited by immune checkpoints can also be expected, and thus it can be usefully used as an immunotherapy method for various cancer diseases related to HLA-G.

The invention discloses a nano vaccine as well as a preparation method and application thereof. The nano vaccine provided by the invention is prepared by fusing a liposome of which the surface is coupled with an inhibitor of an inhibitory immune checkpoint and a cell membrane of a tumor antigen sensitized dendritic cell cultured by utilizing a tumor cell lysate and keyhole limpet hemocyanin. The obtained nano vaccine is uniform in particle size, the outer layer of the nano vaccine is wrapped by a cell membrane, and the nano vaccine has proper surface potential, size and structural flexibility and is beneficial to aggregation in tumors. After the nano vaccine reaches tumor tissues, antigens can be efficiently and directly presented to T lymphocytes through cell membranes of tumor antigen sensitized dendritic cells, a costimulatory signal necessary for T cell activation is fully provided, meanwhile, T cell depletion can be reversed through an immune checkpoint inhibitor, the function of the inhibited T cells is re-excited, and the T cells are activated. The cytotoxic function and the multiplication capacity of the T cells are effectively and specifically recovered through a double-line strategy.

The application relates to a hybridoma cell strain 1B6A2 secreting an anti-fish T lymphocyte surface membrane protein CD28 monoclonal antibody, the hybridoma cell strain 1B6A2 is preserved in the China Center for Type Culture Collection (CCTCC), and the preservation number is CCTCC NO: C202291, and the preservation date is May 5, 2022. The application provides a powerful tool for simulating a second signal in vitro and exploring a CD28-mediated T cell adaptive immune response mechanism.

The combined use of a first antibody molecule that specifically binds to Fc [gamma] RIIb through its Fab region and binds to Fc [gamma] receptor through its Fc region and a second antibody molecule that specifically binds to PD-1 and binds to at least one Fc [gamma] receptor through its Fc region in the treatment of cancer in a patient having tumor-infiltrating T lymphocytes having medium or high PD-1 expression is described, as well as pharmaceutical compositions and kits comprising these two antibody molecules, as well as methods of using these two antibodies to treat cancer. A diagnostic test for identifying patients who benefit from the treatment described herein is also described.

A conditionally active bispecific antibody comprising: an IgG antibody or antibody fragment that binds to human EpCAM protein, the IgG antibody or antibody fragment comprising a light chain variable region having three complementarity-determining regions L1, L2, and L3, and a heavy chain variable region having three complementarity-determining regions H1, H2, and H3; and at least one scFv antibody fragment that binds to a T lymphocyte protein linked to the C-terminus of at least one light chain of the IgG antibody or antibody fragment.

The invention relates to a CLD18A2-targeted T lymphocyte as well as a preparation method and application thereof. The inventor successfully finds a target gene CLD18A2 suitable for developing CAR T cells from a plurality of tumor related genes for the first time, and successfully prepares CLD18A2-targeted CAR T cells, so that a brand new treatment means is provided for pancreatic cancer, gastric cancer and other tumors.

T-cell malignancies are a broad, heterogenous group of diseases and include T-cell lymphomas and T-cell leukemias. T-cell lymphomas are a heterogeneous group of malignancies involving T lymphocytes and generally characterized by a poor prognosis. Among them, cutaneous T-cell lymphomas involve primarily the skin. Mycosis fungoides and Sézary syndrome are the most frequent cutaneous T-cell lymphomas. The inventors showed that both circulating malignant and non-malignant T cells express CD51 in patients with Sézary syndrome. CD51 therefore appears as a useful diagnostic, prognostic and follow-up marker, and as a potential therapeutic target in T-cell lymphomas.