23 results about "T cell immunotherapy" patented technology

The disclosure provides methods of treating a malignancy comprising administering an effective dose of a chimeric antigen receptor genetically modified T cell immunotherapy and methods for manufacturing such immunotherapy. Some aspects of the disclosure relate to methods of determining objective response of a patient to a T cell immunotherapy based on the levels of attributes prior to and after administration of the immunotherapy to the patient.

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.

Disclosed herein is a method of modifying a T cell during T cell activation comprising contacting the T cell with an inhibitor of prolyl hydroxylase. Also disclosed is a method of producing a chimeric antigen receptor (CAR) or T cell receptor (TCR) T cell comprising (i) modifying the T cell during activation of the T cell by contacting the T cell with an inhibitor of prolyl hydroxylase, (i) introducing a CAR or TCR transgene into the modified T cell, and (iii) harvesting the CAR or TCR T cell. In particular, the inhibitor of prolyl hydroxylase is a small molecule prolyl hydroxylase inhibitor, such as 1, 4-DPCA. The harvested CAR or TCR T cells can be used for adoptive T cell immunotherapy of cancer.

The invention belongs to the technical field of T cell immunotherapy drugs, and particularly relates to a TCR for recognizing SNECR tumor cells and application. The TCR comprises an alpha chain variable region and a beta chain variable region, wherein the alpha chain variable region comprises CDR sequences as shown in SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3; the beta chain variable region comprises a CDR sequence as shown in SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11. The TCR is transduced into the T cell, so that the level of the T cell for secreting IFN-gamma cell factors can be improved, thereby inhibiting the proliferation of the SNECR cell or killing the SNECR cell, and further achieving the purposes of effectively inhibiting the growth of the SNECR tumor and treating the SNECR.

The application belongs to the technical field of biological medicine, and particularly relates to a TCR sequence targeting KRAS G12D antigen and application thereof. The CDR3 region of a wild type TCR is rationally designed and optimized through a simulation docking technology, and an optimized TCR with significantly improved affinity is obtained. Experimental results show that the TCR-T cell (human peripheral blood T cell TCR Homo sapiens) can effectively kill solid tumor cells, inhibit tumor growth in vivo and in vitro, improve the T cell immunotherapy effect, and can be used for preparing a cell drug for solid tumors, and has the advantages of high safety, strong targeting, significant effect and the like. The application provides a new drug selection and treatment scheme for the treatment of solid tumors.

The present invention belongs to the technical fields of biomedicine and molecular biology, and particularly relates to a single-chain fragment variable (scFv) targeting human platelet-derived growth factor receptor (PDGFR)-β and use thereof in chimeric antigen receptor (CAR)-T cell immunotherapy. In the present invention, a scFv sequence targeting a human-derived PDGFRβ antigen is first obtained by immunizing a mouse, and then a second-generation CAR is constructed based on this, and additionally a CAR-T cell is obtained via lentivirus infection. The CAR-T cell can effectively kill a PDGFRβ antigen-positive 293T cell. The present invention provides a brand-new idea for eliminating PDGFRβ-positive cells to treat chronic kidney diseases, chronic liver diseases, cardiovascular diseases and various tumor diseases including various organ fibrosis, and has extremely attractive further development value and application prospects.

This invention provides a method for manipulating the CIITA gene to reduce or avoid immune rejection of CD4+ T cells in CAR-T cell immunotherapy. [Solution] The present invention provides a method for knocking out the CIITA gene by introducing a spacer sequence, a nucleic acid encoding the sgRNA, a vector containing the nucleic acid, and a Cas9 nuclease into cells, which specifically targets the CIITA gene.

The application discloses application of ostruthin in enhancing CAR-T cell anti-tumor function, belongs to the technical field of biological medicine, and the ostruthin can promote cell proliferation, inhibit cell exhaustion, promote the secretion of cytokines related to killing cancer cells, and further enhance the anti-tumor function of CAR-T cells in vivo and in vitro as a cell enhancer of CAR-T cells; experimental results show that when ostruthin is combined with CAR-T cells for anti-tumor treatment, compared with ostruthin or CAR-T cells alone, the combination of the two can significantly inhibit the growth of solid tumors. The application provides a new technical means for improving the tumor treatment effect of CAR-T cell immunotherapy.

The present disclosure provides a method for treating a tumor in a subject in need thereof, the method comprising administering to the subject an effective amount of a combination of a CLDN18.2 antagonist and a GUCY2C antagonist or an antagonist of CLDN18.2 and GUCY2C. The disclosure also provides multispecific chimeric antigen receptor constructs, combinations of chimeric antigen receptors, engineered immune cells, and methods of use thereof. The disclosure further relates to the activation and expansion of cells for therapeutic use, especially for chimeric antigen receptor-based T cell immunotherapy.

Provided herein are methods and compositions for modifying the genome of human T cells. Further, the compositions and methods described herein can be used to generate human T cells with altered specificity and functionality, while limiting the side effects associated with T cell therapies. Provided herein is a human T cell that heterologously expresses one or more polypeptides. In some embodiment, the one or more polypeptides, for example, two or more polypeptides, are encoded by a nucleic acid construct inserted into the TCR locus of the cell.

The application discloses a kind of space-time controllable T cell junction based on DNA nanostructure and its construction method and application, belong to DNA nanotechnology field.T cell junction includes six helix bundle paper structure and assembled internal functional layer and external shielding layer on it;Six helix bundle paper structure is assembled using 63 staple chain and M13;The internal functional layer includes nucleic acid-antibody conjugate combined on the four helix extension sequences of the top and bottom of the six helix bundle paper structure, and hand-in-hand palindromic sequence combined on the two helix extension sequences on left and right sides;External shielding layer includes C chain modified serum albumin binding peptide and chain I, and chain I includes pH response i-motif switch.T cell junction of the application has the space-time control ability of pH response and the potential of inducing TCR cluster to enhance T cell activation, has great potential to improve the safety and effectiveness of T cell immunotherapy.

The invention provides a dual immune checkpoint co-blocking agent for targeting EGFR (epidermal growth factor receptor), the blocking agent is prepared into a target polypeptide molecule by an Fmoc solid phase polypeptide synthesis method, and the polypeptide molecule has a self-assembly behavior in a solution containing EGFR protein; the critical assembly concentration of polypeptide molecules triggered by EGFR protein is 18.2 [mu] M, and nanofibers with the diameter of 8.5 nm are formed through the self-assembly behavior; the nanofiber captures membrane cholesterol and induces membrane vesicles to fall off through a high-density hydrophobic area of the nanofiber, so that EGFR and cholesterol are removed at the same time, and the following dual effects are achieved: 1, biochemical immune checkpoint blocking: reduction of EGFR causes reduction of STAT3 phosphorylation level, and further down-regulation of PD-L1 expression; 2, biomechanical immune checkpoints are blocked, wherein cholesterol is removed, so that the rigidity of tumor cell membranes is remarkably improved, and the sensitivity of the tumor cell membranes to mechanical attack of T cells is enhanced; the blocking agent can significantly improve the killing effect of T cell immunotherapy such as CAR-T cells on solid tumors.

Some embodiments of the methods and compositions provided herein include cells having membrane-tethered, IL13 mutein-directed zetakine receptors, such as those which specifically bind to the IL-13 receptor alpha 2 (IL13Ra2) at a 50-fold higher affinity than wildtype IL-13, and methods of cell-based immunotherapy targeting cancer cells, such as cells of solid tumors, using these compositions. In some embodiments, the receptors include spacer regions, such as particular spacer regions designed to provide certain advantages.

The invention provides combination therapies for treating cancer comprising compositions and methods for γδ T cell immunotherapy in combination DDR inhibitors, including but not limited to PARP inhibitors. Preferably, the combination of γδ T cell immunotherapy and PARP inhibitors for the treatment of cancer further includes combinations with other immunotherapies such as immune checkpoint (ICP) blockade therapy and / or DNA damaging agents such as cytotoxic chemotherapeutic agents. Preferably, when the combination of γδ T cell immunotherapy and DDR inhibitor therapy further include chemotherapeutic agents, the γδ T cells are genetically modified to impart resistance to that chemotherapeutic agent.

Disclosed is a CAR-T cell with good blood-brain barrier permeability, a product, and use thereof, relating to the technical field of treatment of central nervous system diseases. Based on the study on CAR-T cell immunotherapy for central nervous system diseases, this disclosure provides a CAR-T cell with good blood-brain barrier permeability and a corresponding drug for treating or improving the central nervous system diseases. The CAR-T cell targets B-cell maturation antigens and highly expresses a chemokine receptor CXCR3 and chemokines CCL1, CCL3, and CCL4. This disclosure further provides a product for detecting and judging the blood-brain barrier permeability of the CAR-T cell, such as probes, reagents, and kits, which can accurately detect and judge the blood-brain barrier permeability of a specific CAR-T cell.

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 invention provides improved T cell compositions and methods for manufacturing T cells. More particularly, the invention provides methods of T cell manufacturing that result in adoptive T cell immunotherapies with improved survival, expansion, and persistence in vivo.

This invention provides a lipid compound and its applications, the results of which are shown in Formula I. The lipid compound provided by this invention can be used for targeted delivery of bioactive molecules to splenic T cells, particularly suitable for transporting negatively charged nucleic acid molecules, such as mRNA, providing a potential delivery strategy for in vivo specific gene editing of T cells. This invention also provides a bioactive substance delivery system comprising the lipid compound, which is loaded with bioactive substances. The bioactive substance delivery system of this invention, after intravenous administration, can efficiently target spleen tissue and selectively deliver active substances to T cells within the spleen, achieving efficient T cell transfection and immune activation. The delivery system of this invention has a simple synthesis process and strong structural tunability, and has broad application prospects in the fields of T cell immunotherapy and gene therapy.

The invention belongs to the technical field of T cell immunotherapy drugs, and particularly relates to a TCR (T cell receptor) of a targeted polypeptide-HLA-B * 40: 01-compound or an antigen binding fragment of the TCR and application of the TCR. The TCR or the antigen binding fragment thereof comprises an alpha chain variable region and a beta chain variable region, wherein the alpha chain variable region comprises a CDR sequence as shown in SEQ ID NO: 1-3; and the beta chain variable region comprises a CDR sequence as shown in SEQ ID NO: 9-11. The TCR is transduced into T cells, has very strong specificity on tumor cells expressing tumor-associated antigen CTCFL, and can improve the level of the T cells secreting IFN-gamma cytokines, thereby inhibiting proliferation of the tumor cells expressing CTCFL or killing the tumor cells expressing CTCFL, and further achieving the purposes of effectively inhibiting tumor growth and treating tumors.

The application belongs to the field of biotechnology and immunotherapy, and particularly relates to an additive composition for enhancing the killing activity of CAR-CD19 T cells on B cell malignancies, a culture medium and application thereof. The composition is composed of SIRT1 activator SRT2104 and antioxidant ergothioneine, and the final concentrations of the two in the T cell culture medium are 1-10 muM and 5-50 muM respectively. In vitro killing experiments show that the killing efficiency of the composition on Nalm6 tumor cells is significantly better than that of SRT2104 or ergothioneine alone, and the composition has a significant synergistic effect, thereby providing a new solution for improving the CAR-T cell immunotherapy effect.

This invention discloses a method for preparing T cells for tumor therapy by reducing the content or activity of SARDH protein. The method for preparing T cells for tumor therapy includes: reducing the content or activity of SARDH protein in recipient T cells, or reducing the expression level of the SARDH gene in recipient T cells, or knocking out the SARDH gene in recipient T cells, to obtain target T cells for tumor therapy. This invention discovers a novel target with significant innovative mechanisms of action. By reducing the content or activity of SARDH protein, or reducing the expression level of its encoding gene, or knocking out its encoding gene, the efficacy of T cell immunotherapy can be further improved. This invention provides a new perspective on elucidating the mechanism by which T cells enter tumors and become exhausted.

The application discloses modified target HPV enhanced immune cells and medical uses thereof. The application provides T cell receptors or fragments thereof targeting E7 antigens of HPV and medical uses thereof. In addition, the application also provides modified immune cells expressing TCRs targeting HPV and conversion costimulatory molecules and medical uses thereof. The modified immune cells of the application replace the intracellular inhibitory signal domain of the immunosuppressive receptor with the intracellular activation signal domain of the costimulatory molecule, convert the inhibitory signal induced by the immunosuppressive factor or ligand binding into an activation signal, effectively block the cell exhaustion induced by the immunosuppressive molecule, and increase the release of cytokines, the cell proliferation capacity and the tumor cell killing capacity. The application is expected to overcome a series of problems such as tumor heterogeneity, difficulty in penetrating tumor barriers, short action time and local immunosuppressive microenvironment faced by adoptive T cell immunotherapy.

Some embodiments of the methods and compositions provided herein include cells having membrane-tethered. IL13 mutein-directed zetakine receptors, such as those which specifically bind to the IL-13 receptor alpha 2 (IL13Ra2) at a 50-fold higher affinity than wild-type IL-13, and methods of cell-based immunotherapy targeting cancer cells, such as cells of solid tumors, using these compositions. In some embodiments, the receptors include spacer regions, such as particular spacer regions designed to provide certain advantages.