99results about How to "Improve tumor killing ability" patented technology

The invention relates to an engineered immune cell, and the engineered immune cell expresses (i) a chimeric receptor, and (ii) exogenous CCL3, CCL4 and / or CCL5. The invention further provides application of the engineered immune cell to treatment of cancers, infections or autoimmune diseases. Compared with a traditional engineered immune cell, the engineered immune cell provided by the invention has the remarkably improved tumor killing activity.

The invention belongs to the biological medicine field, and relates to a fusion protein efficiently combined with a PD-1 and a VEGF, and a coding sequence and a use thereof. Specifically, the invention relates to the separated fusion protein comprising the following peptide fragments: (1) a human PD-L2 extracellular region peptide fragment; (2) a peptide fragment of a second immunoglobulin-like structural domain of a human FLT-1 extracellular region or / and a peptide fragment of a third immunoglobulin-like structural domain of a KDR extracellular region; and optionally (3) a human immunoglobulin Fc fragment. The fusion protein can inhibit the growth of tumor cells, promotes the death of the tumor cells, inhibits T cell inactivation, and enhances a tumor killing ability.

The invention discloses a preparation method of antitumor adoptive immune cells. The method comprises the following steps of: sampling and separating a single peripheral blood karyocyte; and adding a cell factor for inducting and culturing to obtain a cytokine induced kill cell (CIK), wherein the cell factor comprises CD28. In a CIK induced system, the cell factor CD28 is induced, so that the inducing effect is enhanced, and the cell proliferation multiple is increased simultaneously.

The invention relates to a gel injection combining a molecular targeted drug and a cytotoxic drug. The gel injection comprises a small molecular targeted drug, a traditional cytotoxic drug, a temperature-sensitive material, a solvent and pharmaceutical excipients, wherein the temperature-sensitive material is selected from poloxamer, polylacticacid-polyethylene glycol-polylactic acid or polyglycolide lactide-polyethylene glycol-polyglycolide lactide and the like; the solvent is selected from water, brine salt or 5% glucose aqueous solution and the like, the prepared gel injection can be injected intratumorally or peritumorally, the anti-tumor effect is obvious, and the side effects are fewer.

The invention belongs to the technical field of cell immunology and provides a novel preparation method of a dendritic cell (DC) vaccine. According to the novel preparation method of the dendritic cell (DC) vaccine, while tumor antigen is loaded, exogenous Bcl-2 mRNA and IL-12P70 mRNA are transferred into DC cells in an electrotransfection manner. The method has the advantages that the prepared DCcells have higher vitality and longer survival time, and can secrete abundant IL-12, therefore, the antigen presenting capacity of the DC is remarkably increased, and the specific immune response ofthe antigen is effectively induced. The DC vaccine prepared by the method is mainly used for treatment for tumor or prevention of cancer high-risk people, and the preparation method has the features that the preparation process is simple, the cost is low, the specificity is strong, the curative effects are significant, etc.

The invention provides a separated recombinant oncolytic adenovirus, a drug composition and application of the separated recombinant oncolytic adenovirus to a drug for treating tumor and / or cancer. The recombinant oncolytic adenovirus is a selective replication type oncolytic adenovirus, and a genome of the recombinant oncolytic adenovirus is integrated with a coded sequence of exogenous shRNA capable of inhibiting PDL1 expression in tumor cells. The replication ability of the separated recombinant oncolytic adenovirus in normal primary cells is far lower than that of the separated recombinantoncolytic adenovirus in the tumor cells, the high-expression PDL1 protein level in the tumor cells can be significantly lowered by expressed shPDL1, and thus the oncolytic killing effect of an oncolytic virus and the antitumor immunostimulation effect of T lymphocyte achieve a synergetic effect.

The present invention relates to an engineered immune cell expressing (i) a cell surface molecule that specifically recognizes a ligand, (ii) an exogenous interleukin, and (iii) an exogenous Flt3L, XCL2, and / or XCL1. The invention also provides the use of the engineered immune cell in the treatment of cancer, infection or autoimmune disease. Compared with the traditional engineered immune cell, the engineered immune cell has remarkably improved tumor killing activity.

The invention provides a high-efficiency amplification culture solution for tumor infiltration lymphocytes. The culture solution contains IL-2, IL-12, anti-CD28 and anti-CTLA-4. Compared with the prior art, the high-efficiency amplification culture solution has the advantages that a combined serum-free culture medium containing IL-2, IL-12, anti-CD28, anti-CTLA-4 and other cell factors is adopted, the amplification efficiency of TIL cells is obviously improved, and the amplification efficiency is about 3-10 times higher than the amplification efficiency of a common amplification culture solution; moreover, an inhibitory function of Treg lymphocytes on cytotoxic T lymphocytes can be effectively achieved, and the amplified lymphocyte has an extremely strong tumor killing effect.

The invention belongs to the field of biomedical detection, and in particular relates to a culture method of tumor specific TIL cells. According to the culture method of the tumor specific TIL cells disclosed by the invention, the tumor specific TIL cells can be acquired by screening specific magnetic beads twice. The method disclosed by the invention is simple in operation, and is capable of efficiently obtaining the tumor specific TIL cells through multiplication culture and greatly enhancing the tumor-cytotoxicity effect of the TIL cells; and meanwhile, through serum-free culture, the method can solve the potential risks of transmission of viruses and other dangers in the prior art, so as to provide a foundation for extensive application in the future.

The invention provides a culture medium for human-derived T lymphocytes. Each 1L of the culture medium comprises the following components: 80-120 mL of human AB serum, 7-15 mL of an MEM vitamin solution, 7-12 mM of N-acetyl-L-cysteine, 1.6-2.5 mM of glutamine or a derivative, 0.8-1.2 mM of sodium pyruvate, 15-25 mM of 4-hydroxyethyl piperazine sodium esilate, 4-6 mu g of IL-7, 6-9 mu g of IL-15 or heterodimer thereof, and the balance of X-VIVO basic culture medium, wherein the glutamine or the derivative thereof comprises glutamine or L-alanyl-L-glutamine. The culture medium can be used for culturing antigen specific T lymphocytes, the cell proliferation rate of the antigen specific T lymphocytes can be increased, and the tumor killing ability can be high. The invention further provides a preparation method and application of the culture medium.

The invention discloses a metal organic framework composite nanomaterial with targeting property and pH responsiveness as well as a preparation method and application of the metal organic framework composite nanomaterial. The metal organic framework composite nanomaterial is prepared from protein-loaded ZIF-8 metal organic framework nano-particles, calcium carbonate structures wrapping the ZIF-8 nano-particles and aptamers fixed to calcium carbonate structures. The preparation method is simple and convenient to operate, and damage to protein activity is avoided. The composite nano material provided by the invention has good protein loading capacity and targeting performance, and can gradually release contents in a low pH environment. The metal organic framework composite nanomaterial disclosed by the invention can also target T cells to increase the number of intracellular anti-tumor active substances, and can be developed into a novel anti-tumor biological therapy.

The invention discloses a construction method of a chimeric antigen receptor double-negative T cell. The construction method comprises the following steps: according to characteristics of CD3<+> / CD4<-> / CD8<->double-negative T cell, selecting the purified CD3<+> / CD4<-> / CD8<->double-negative T cell in vitro, and utilizing the synergistic principle of multiple cell factor signal channels and a TCR signal channel to screen out an in-vitro culture scheme suitable for activation and virus transfection of the double-negative T cell. The in-vitro culture scheme can quickly and controllably activate the double-negative T cell, expresses the specific chimeric antigen receptor on the double-negative T cell through a lentiviral transfection technology at high efficiency, preparing a CAR-DN-T cell, enables the CAR-DN-T cell to specifically identify the tumor cell corresponding to the chimeric antigen receptor, promotes the CAR-DN-T cell to be further activated and proliferated, and quickly kills and wounds the tumor cell. According to the construction method disclosed by the invention, the prepared CAR-DN-T cell is from homologous variants of other healthy donators, so that the preparation of the cell gets rid of limitation of the current illness situation of a patient, the cell can be prepared on a large scale in advance, and the patient can be subjected to low-dosage re-transfusion treatment for multiple times according to the clinical diagnosis result at any time.

The present invention provides a therapeutic agent comprising isolated recombinant oncolytic adenoviruses and immune cells and uses thereof. The therapeutic agent comprises: a tfirst composition, wherein the first composition comprises a first active ingredient located in a first pharmaceutically acceptable carrier, wherein the first active component comprises an isolated recombinant oncolytic adenovirus, the recombinant oncolytic adenovirus is a selective replication type oncolytic adenovirus, and a coding sequence of exogenous shRNA capable of inhibiting PDL1 expression in tumor cells is integrated in a genome of the recombinant oncolytic adenovirus; and a second composition wherein the second composition comprises a second active ingredient located in a second pharmaceutically acceptable carrier, the second active ingredient comprising T cell receptor modified immune cells or chimeric antigen receptor modified immune cells. According to the invention, the oncolytic adenovirus and the immune cells are combined for use to realize a synergistic treatment effect, and the administration mode enriches the treatment mode and treatment means of tumor treatment.

The present invention relates to an engineered immune cell, which is capable of expressing a chimeric antigen receptor, an exogenous Flt3L gene and a DLL1 gene, and optionally an XCL1 and / or XCL2 gene. The invention also provides the use of the engineered immune cell in the treatment of cancer, infection or autoimmune disease. Compared with a traditional CAR cell, the engineered immune cell has the advantage that the tumor killing activity is remarkably improved.

The present invention relates to: —use of a 2,3-dihydroimidazo[1,2-c]quinazoline compound, or of a pharmaceutical composition containing same, as a sole active agent, or of a combination of a) said compound or a pharmaceutical composition containing said compound and b) one or more further active agents, for the preparation of a medicament for the treatment or prophylaxis of cancer; —combinations of a) said compound and b) one or more further active agents; —a pharmaceutical composition comprising said compound as a sole active agent for the treatment of breast cancer; —a pharmaceutical composition comprising a combination of a) said compound and b) one or more further active agents; —use of biomarkers involved in the modification of Bel expression, HER family expression and / or activation, PIK3CA signaling and / or loss of PTEN for predicting the sensitivity and / or resistance of a cancer patient to said compound and providing a rationale-based synergistic combination as defined herein to increase sensitivity and / or to overcome resistance; and —a method of determining the level of a component of one or more of Bcl expression, HER family expression and / or activation, PIK3CA signaling and / or loss of PTEN.

The present invention relates to a method for identifying a substance capable of disrupting an interaction between (i) a herpes simplex virus (HSV) ICP34.5 polypeptide or a homologue thereof, or a derivative thereof, and (ii) proliferating cell nuclear antigen (PCNA) or a homologue thereof, or a derivative thereof. The method comprises: (a) providing an HSV ICP34.5 polypeptide or a homologue thereof, or a derivative thereof, as a first component; (b) providing PCNA, or a homologue thereof, or a derivative thereof, as a second component; (c) contacting the two components with a substance to be tested under conditions that would permit the two components to interact in the absence of the substance; and (d) determining whether the substance disrupts the interaction between the first and second components.

The invention provides a fourth-generation CAR-T cell and an application thereof. The fourth-generation CAR-T cell expresses a chimeric antigen receptor specifically binding to an antigen, a secretoryIL-7 and an NFAT regulatory CCL19,wherein the signal peptide of the IL-7 is an IL-10 signal peptide; and a promoter of the CCL19 is an NFAT regulatory promoter. According to the invention, the original signal peptide of the IL-7 is changed into the signal peptide of T cell secretory protein IL-10, and the NFAT regulatory promoter is adopted as the promoter of CCL19, so that the CAR-T cell can secrete the IL-7 to the outside of the cell and conditionally express the CCL19, the proliferation of the CAR-T cell is promoted, immune cells are recruited to the inside of tumors to the greatest extent, and the anti-tumor efficacy of the CAR-T is obviously improved.

The invention belongs to the field of biological medicines, and discloses a drug containing arsenic nanoparticles, which comprises transition metal, arsenic and protein, and the protein is a carrier and is loaded with the transition metal and the arsenic. According to the synthesized drug containing arsenic nanoparticles, single protein serves as a template, the particle size of the synthesized drug is smaller than 15 nm, the in-vivo circulation time can be prolonged due to the small particle size, and uptake of tumor to the drug is increased. The drug containing the arsenic nanoparticles hasan acid-responsive release characteristic, and can release the drug for a tumor microenvironment and tumor cells in a targeting manner, so that the side effect caused by non-specific release of the drug is reduced, the local drug concentration of the tumor can be improved, and the tumor killing effect is enhanced. Meanwhile, the drug containing the arsenic nanoparticles is simple in synthesis mode, mild in reaction condition, cheap and easily available in reaction raw materials, low in purification cost and small in environmental pollution, does not need to use an organic solvent, has clinicalconversion potential, and can be produced in a large-scale expanded manner.

The invention discloses a bispecific antibody as well as a preparation method and application thereof. The bispecific antibody comprises the following components from a N terminal to a C terminal: a liver cancer cell surface antigen GPC3 corresponding antibody; a heavy chain constant region; and an immune cell surface antigen corresponding antibody. The bispecific antibody disclosed by the invention can simultaneously recognize a liver cancer cell surface antigen and an immune cell surface antigen, and realizes targeted killing of liver cancer cells by immune cells; at the same time, the bispecific antibody is used as a bridge to connect the immune cells and the liver cancer cells, can increase contact time of the immune cells and the liver cancer cells, and effectively enhance a killing effect of the immune cells on the liver cancer cells; and since the two antigens are combined at the same time, the bispecific antibody disclosed by the invention can effectively activate the immune cells, close the distance between the immune cells and the liver cancer cells, increase an effector-target ratio, and enhance tumoricidal ability of the immune cells.

The present invention method of malignant tumor broad-spectrum gene engineering nano vaccine adopts the following steps: adopting tumor specific common antigen gene melanin tumor antigen-I (MAGE-1) and biological immunoadjuvant heat shock protein 70(Hsp70) to make gene connection to form fusion gene (MAGE-1-Hsp70), utilizing colibacillus expression, separation and purification to obtain MAGE-1-Hsp70 fusion protein, and utilizing denaturation and renaturation to obtain fusion protein with high activity, combining said fusion protein and superantigen staphylococcal enterotoxin A to form complex antigenic compound; preparing nano liposome, covering the complex antigenic compound, utilizing molecular connection of N-hydroxysuccinimide ester and Hsp70 to form N-Hsp70, and inserting it into outer layer of nano liposome phospholipid membrane.

The invention discloses an EGFR (epidermal growth factor receptor)-specific chimeric antigen receptor and application thereof. The EGFR-specific chimeric antigen receptor comprises a transmembrane signal region, an extracellular recognition region, a hinge region, a transmembrane region and an intracellular signal transduction region, which are connected in sequence. A CAR-T with the surface modified by the EGFR-specific chimeric antigen receptor has a strong tumor-specific antigen activation effect, a cytokine secretion function and a tumor-killing ability for triple negative breast cancer; the in-vitro killing efficiency is more than 90% under a low effector-to-target ratio; animal experiments verify the remarkable effective inhibitory effect of the CAR-T, the CAR-T has a remarkable tumor suppressive effect in in-vivo experiments, and accordingly, it is indicated that the CAR-T of the EGFR-specific chimeric antigen receptor has high applicability to the triple negative breast cancer.

The invention discloses a copper composite based intelligent nanometer material and a preparation method and antitumor application thereof, and belongs to the fields of a nanometer material and preparation thereof. A copper composite is synthesized firstly, the copper composite and near infrared fluorescent dyes are loaded to an organic phase change material together, and a light control intelligent nanometer material being uniform to disperse and good in light heat efficiency can be prepared. The nanometer material can cause DNA injury and apoptosis through light control target cell nucleus,an EMT process is restrained, the transfer ability of tumor cells is destroyed, and the copper composite based intelligent nanometer material is hopeful to be used for antitumor research.

The present invention relates to a cell modification method for modifying human or mammal immune cells, especially effector cells outside the human or mammal body, wherein in a first step at least one encapsulated substance, preferably an active pharmaceutical ingredient, is introduced in and / or arranged on isolated human or mammal immune cells and wherein in a second step prior to or after the introduction of said at least one substance the cytotoxic effector function of the isolated immune cells is enhanced. The present invention also relates to a correspondingly modified human or mammal immune cell and to a cell modification device.

The invention provides a double-target chimeric antigen receptor targeting CLL1 and a NKG2D ligand and application thereof. The double-target chimeric antigen receptor comprises a signal peptide, an antigen binding structural domain, a hinge region, a transmembrane structural domain and a signal transduction structural domain, and the antigen binding domain comprises an anti-CLL1 antibody and NKG2D. The CAR molecule simultaneously targeting CLL1 and the NKG2D ligand is constructed, the effect of comprehensively targeting acute myelogenous leukemia cells is achieved, the CAR-T cells for expressing the double-target CAR targeting CLL1 and the NKG2D ligand are remarkable in tumor removal effect, the antigen escape phenomenon is avoided, and the CAR molecule has important significance in the field of tumor treatment.

The invention discloses a recombinant CAR19-IL24 gene, a lentiviral vector, a CAR19-IL24-T cell and application of the recombinant CAR19-IL24 gene, lentiviral vector and CAR19-IL24-T cell.

The invention belongs to the technical field of biological medicines, and particularly relates to a FasL-CAR fusion protein, a T cell containing the FasL-CAR fusion protein, and a preparation method and an application thereof. The T cell expressing the FasL-CAR fusion protein has the property of enhancing FasL protein expression, and the ability of a FasL / Fas signal pathway of the T cell to inducetumor cell apoptosis is enhanced, so that the ability of the CAR-T cell to kill tumor cells is enhanced, and the possibility of tumor recurrence after treatment is reduced. When the FastL-CAR fusionprotein and the T cell expressing the FastL-CAR fusion protein are applied to a medicine for treating tumors, an effective way for treating cancers can be provided.

The invention provides a recombinant staphylococcal enterotoxin I oral preparation, the recombinant staphylococcal enterotoxin I has SEQ ID NO.1 amino acid sequence, and the oral preparation further comprises a pharmaceutical allowable drug excipient or a carrier. The oral preparation proves that the protein can enter the systemic blood circulation by penetrating epithelial cells on small intestine with the form of complete molecules and maintain the super-antigen activity for promoting the spleen lymphocyte proliferation and inhibiting the growth of tumor cells, as well as the application in the preparation of drugs for treating malignant tumors and other serious complications by the Caco-2 monolayer cell transmembrane transport test.