38 results about "T cell immunotherapy" patented technology

The invention relates to the field of medical detection, and particularly provides a diagnostic model for predicting prognosis of gastric cancer CAR-T cellular immunotherapy and application of the diagnostic model. According to the present invention, the content and the spatial distribution map of the CLDN18.2 positive gastric cancer tissue sample microenvironment component are systematically analyzed by integrating the multiple fluorescence immunohistochemical detection and the full-slice digital imaging quantitative analysis method for the first time; through multi-dimensional evaluation of a tumor microenvironment under the treatment background of a targeted CLDN18.2 chimeric antigen receptor T cell immunotherapy CT041, a diagnosis model for predicting the prognosis of the gastric cancer CAR-T cell immunotherapy is established for the first time, accurate screening of benefited people and risk stratification before treatment are realized, treatment selection is guided, and the treatment effect is improved.

The disclosure provides methods of treating a malignancy comprising administering an effective dose of an immune cell therapy (e.g., 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 an immune cell immunotherapy based on the levels of patient and product attributes prior to and after administration of the immunotherapy to the patient.

The invention discloses a time-space controllable T cell adapter based on a DNA nanostructure as well as a construction method and application of the time-space controllable T cell adapter, and belongs to the field of DNA nanotechnology. The T cell adapter comprises a six-spiral-bundle paper folding structure, and an internal functional layer and an external shielding layer which are assembled on the six-spiral-bundle paper folding structure; the six-spiral bundle paper folding structure is formed by assembling 63 staple chains and M13 in total; the internal functional layer comprises nucleic acid-antibody conjugates which are combined on four spiral extension sequences at the top and the bottom of the six-spiral bundle origami structure, and hand-in-hand palindromic sequences which are combined on two spiral extension sequences at the left side and the right side; the outer shielding layer comprises a C-chain modified serum albumin binding peptide and a chain I, and the chain I comprises a pH-responsive i-motif switch. The T cell adapter disclosed by the invention has the space-time control capability of pH response and the potential of inducing TCR clustering to enhance T cell activation, and has huge potential in the aspect of improving the safety and effectiveness of T cell immunotherapy.

The present invention relates to the field of medical testing. Specifically, the present invention provides a diagnostic model for predicting the prognosis of CAR-T cell immunotherapy for gastric cancer and its application. For the first time, the present invention systematically analyzed the content and spatial distribution map of the microenvironment components of CLDN18.2-positive gastric cancer tissue samples by integrating multiple fluorescent immunohistochemistry detection and whole-slice digital imaging quantitative analysis methods. Through multidimensional evaluation of the tumor microenvironment under the treatment background of CT041, a diagnostic model for predicting the prognosis of CAR-T cell immunotherapy for gastric cancer was established for the first time, which enables accurate screening of beneficiary populations and risk stratification before treatment, guides treatment selection, and improves treatment efficacy.

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 invention relates to a human papillomavirus antigen peptide and its application, belonging to the technical field of immunomedicine. The antigen peptide comprises the amino acid sequence shown in SEQ ID NO.1, or a small peptide having more than 90% similarity to the amino acid sequence shown in SEQ ID NO.1. The above-mentioned human papillomavirus antigen peptide is a new target located in the E7 gene of the HPV16 genome. This target is not expressed in normal human tissues during viral genome expression and can be used as an antigen target for applications in reagents, drugs, or vaccines for the diagnosis, treatment, and prognosis determination of clinical HPV16 / 18 infections or HPV16 / 18-positive tumors such as cervical cancer, esophageal cancer, head and neck cancer, oropharyngeal cancer, anogenital cancer, etc. For example, through adoptive T cell immunotherapy, it may bring new treatment possibilities to patients with advanced recurrent cervical cancer.

The disclosure provides methods of treating a malignancy comprising administering an effective dose of a chimeric receptor (e.g., CAR or TCR) genetically modified T cell immunotherapy. Some aspects of the disclosure relate to methods of characterizing the pre-infusion tumor microenvironment and determining an effective dose of a T cell immunotherapy.

The invention discloses a T cell receptor for recognizing HPV16E7 presented by an HLA-B1518 molecule and application of the T cell receptor. The T cell receptor comprises a TCR alpha chain variable domain and a TCR beta chain variable domain, and amino acid sequences of three complementary determining regions of the TCR alpha chain variable domain are shown as SEQ ID NO: 9-11; the amino acid sequences of the three complementary determining regions of the TCR beta chain variable domain are as shown in SEQ ID NO: 12-14. The invention provides a T cell receptor (TCR). The TCR can be specifically combined with HPV16E7 presented by an HLA-B1518 molecule; t cells transduction of the TCR can generate a powerful killing effect on SiHa cells; and a new way is provided for TCR-T cell immunotherapy of cervical cancer.

The present invention relates to a P2Y purinoceptor 2 (P2RY2) activity modulator for use in T cell immunotherapy. The present invention further relates to a polynucleotide encoding a P2RY2 activity modulator and to a host cell comprising the P2RY2 activity modulator for use in T cell immunotherapy. Furthermore, the present invention relates to a method of identifying 5 a subject amenable to T cell immunotherapy comprising (A) determining in a sample of said subject the activity of P2RY2; (B) comparing the activity determined in step (A) to a reference; and identifying a subject amenable to T cell immunotherapy based on the comparison of step (B), as well as to a method for identifying a P2RY2 activity modulator, said method comprising (I) contacting a host cell with a candidate compound suspected to be a P2RY2 activity 10 modulator; (II) determining B7-H3 activity in said host cell; (III) comparing the B7-H3 activity determined in step (II) to a control; and (IV) identifying a P2RY2 activity modulator based on the comparison in step (III).

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.

The present disclosure provides methods, compositions, and kits for improving one or more properties of T cells, such as therapeutic T cells engineered to express an antigen-specific binding protein. Disclosed embodiments include methods that comprise introducing to T cells (e.g., CD8+ T cells, CD4+ T cells, or both) with (1) TGFβ (or a functional analog, mimic, or fragment thereof) and (2) an inhibitor of LSD1 activity and / or expression. The present disclosure also provides methods comprising increasing expression or activity of GPX4 in T cells, which, as taught herein, can improve T cell functionalities.

The invention relates to a targeted B7-H3 chimeric antigen receptor-T cell for expressing CXCL10 and application of the targeted B7-H3 chimeric antigen receptor-T cell in tumor treatment. The targeted B7-H3 chimeric antigen receptor-T cell comprises a targeted B7-H3 chimeric antigen receptor, a chemotactic factor CXCL10 and application of the targeted B7-H3 chimeric antigen receptor-T cell in tumor treatment. The chemotactic factor provided by the invention can effectively promote the effect of CAR-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 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 relates to the technical field of T cell immunotherapy drugs, in particular to a specific TCR CDR3 region sequence and application thereof. According to the invention, killer T cells are obtained by adopting an in-vitro antigen presentation method, antigen-specific killer T cells are sorted by a tetramer technology, and main TCR clones are obtained by TCR sequencing. A high variable loop region CDR3 of a main TCR chain is subjected to alanine substitution, a sequence with higher affinity is screened, and the sequence is suitable for all target antigens. The transformation of the natural sequence is beneficial to further understanding how the TCR affinity affects antigen recognition and TCR cross reaction and distinguishing TCR biochemical recognition and T cell function recognition, so that the TCR-based immunotherapy is more reasonably designed, and the TCR treatment safety is improved.

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 invention discloses a thymus decellularized scaffold as well as a preparation method, a kit and application thereof. The method comprises the following steps: 1) flushing thymus with a cleaning agent; 2) washing the cleaned thymus with a detergent A; 3) washing the washed thymus with a detergent B; 4) washing the washed thymus with a preservative; 5) cleaning the flushed thymus by using a cleaning agent; and 6) adding a preservative to prepare the thymus decellularized scaffold. The cleaning agent contains EDTA, antibiotics and PBS; the detergent A contains lauryl sodium sulfate and antibiotics; the detergent B contains anhydrous magnesium sulfate, anhydrous calcium chloride, Triton X-100 and antibiotics; and the preservative contains antibiotics and PBS. The method for amplifying thymus stromal cells in vitro based on the thymus decellularized scaffold is beneficial to directional induction of development and differentiation of hematopoietic stem progenitor cells into T cells, and has wide application potentials in large-scale culture of T cells in the future and in the field of T cell immunotherapy.

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 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 provides improved anti-BCMA CAR T cell compositions and methods for producing anti-BCMA CAR T cell therapies. More specifically, the present invention relates to improved methods for producing anti-BCMA CAR T cells that produce stronger, longer-lasting, and more effective adoptive T cell immunotherapy. In certain embodiments, the cells are produced from subjects with multiple myeloma or lymphoma.