66 results about "Granzyme B" patented technology

T cell immune responses are enhanced by presentation of antigen to CD8+ T cells using a chimeric nucleic acid immunogen or vaccine that links DNA encoding an antigen with DNA encoding a polypeptide that targets or translocates the antigenic polypeptide to which it is fused (immunogenicity-potentiating polypeptides or “IPP”). By inhibiting apoptosis in the vicinity of a T cell responses to such a nucleic acid immunogen, even more potent immune responses are attained. The present strategy prolongs the survival of DNA-transduced cells, including dendritic cells (DCs), thereby enhancing the priming of antigen-specific T cells and increase potency. Co-delivery of DNA encoding an inhibitor of apoptosis, including (a) BCL-xL, (b) BCL-2, (c) XIAP, (d) dominant negative caspase-9, or (e) dominant negative caspase-8, or (f) serine protease inhibitor 6 (SPI-6) which inhibits granzyme B, with DNA encoding an antigen, prolongs the survival of transduced DCs and results in significant enhancement of antigenspecific T cell immune responses that provide potent antitumor effects. Thus, co-administration of a DNA vaccine encoding antigen linked to an IPP along with one or more DNA constructs encoding an anti-apoptotic protein provides a novel way to enhance vaccine potency.

The 121-amino acid isoform of vascular endothelial growth factor (VEGF121) is linked by a flexible G4S tether to a cytotoxic molecule such as toxin gelonin or granzyme B and expressed as a soluble fusion protein. The VEGF12, fusion protein exhibits significant anti-tumor vascular-ablative effects that inhibit the growth of primary tumors and inhibit metastatic spread and vascularization of metastases. The VEGF121 fusion protein also target osteoclast precursor cells in vivo and inhibits osteoclastogenesis.

Cell-targeted serine protease constructs are provided. Such constructs can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer). In some aspects, recombinant serine proteases, such as Granzyme B polypeptides, are provided that exhibit improved stability and cell toxicity. Methods and compositions for treating lapatinib or trastuzumab-resistant cancers are also provided.

The invention belongs to the pharmacological field of gene engineering, and provides a group of protein derivatives of human granzyme B by adopting gene engineering technology. The group of protein derivatives of the human granzyme B comprises GrB-G4S-GnRH (GrBLG) and mGrB-C4S-GnRH (mGrBLG) which are targeted fusion proteins formed by connecting human matured granzyme B (GrB) and mutagenic human matured granzyme B (mGrB) with human gonadotropin-releasing hormone (GnRH) through flexible connecting short peptide GlyGlyGlyGlySer (G4S) respectively and which can be combined with human GnRH receptors (GnRHR) on the surfaces of cells through ligand human GnRH. The mGrB eliminates the functions of the combination through a personal 'electrostatic exchange-absorption mode' and the entering into target cells of the prior GrB, and simultaneously reserves the enzymatic activity and the cytocidal function of the GrB. The invention provides experimental evidences for peculiarly targeted-killing GnRHR positive cells and minimizing toxic side effect by the fusion proteins, and shows the use of the group of protein derivatives of the human granzyme B in the targeted therapy on the positive adenocarcinoma of a type of gonadotropin-releasing hormone receptors.

The present invention encompasses compounds of Formula (I) and pharmaceutically acceptable salts or hydrates thereof. The compounds are inhibitors of granzyme B and are useful for treating autoimmune and chronic inflammatory diseases. Pharmaceutical compositions and methods of use are also included.

The present invention relates to a cell line of lymphocytes comprising γδ T cells, composition and production method thereof, and medical use namely for the use in medicine, namely in cancer immunotherapy.The cell line comprise a sample of human peripheral blood Vδ1+γδ T cells expressing functional natural cytotoxicity receptors (NCRs). These Vδ1+ NCR+ T lymphocytes can directly mediate killing of leukemia cell lines and chronic lymphocytic leukemia patient neoplastic cells.The present invention shows that human Vδ1+ NCR+ T cells can be differentiated and expanded from total γδ peripheral blood lymphocytes (PBLs), upon regular in vitro or ex vivo stimulation with γδTCR agonists and γc-family cytokines. This subset surprisingly expresses NKp30, NKp44 and NKp46, and high levels of Granzyme B that associate with highly enhanced cytotoxicity against lymphoid leukemias.

The present invention relates to a method for diagnosis, detection, or prognosis of sepsis and its severity. More specifically, this invention uses the presence and amount of granzyme B in platelets as a marker for sepsis.

Covalent Granzyme B inhibitors, compositions that include the compounds, and methods for using the compounds. A method for treating cutaneous scleroderma, epidermolysis bullosa, radiation dermatitis, alopecia areata, and discoid lupus erythematosus are provided.

Proline compounds as Granzyme B inhibitors, compositions that include the compounds, and methods for using the compounds. Methods for treating cutaneous scleroderma, epidermolysis bullosa, radiation dermatitis, alopecia areata, and discoid lupus erythematosus are provided.

Pyrrole compounds as Granzyme B inhibitors, compositions that include the compounds, and methods for using the compounds. Method for treating cutaneous scleroderma, epidermolysis bullosa, radiation dermatitis, alopecia areata, and discoid lupus erythematosus are provided.

Methods of promoting wound healing in a subject is disclosed. The method include applying a Granzyme B (Granzyme B) inhibitor to the wound. The wound may be a skin wound. The Granzyme B inhibitor may be comprised of nucleic acids, or peptides, including but not limited to antibodies, or small molecules.

Granzyme B inhibitor compounds, compositions that include the compounds, and methods for using the compounds. The compounds of the invention have advantageous water solubility and effectively inhibit Granzyme B.

The invention relates to application of a hemsley rockvine root extract in preparing a tumor immunity therapeutic drug and a human gamma delta T cell proliferation agent, belonging to the technical field of medicine and biology. The hemsley rockvine root extract can notably accelerate proliferation of human gamma delta T cells, improves the expressions of porforin, CD107a and granzyme B of the gamma delta T cells, and has certain dose dependence; and the gamma delta T cells treated by the hemsley rockvine root extract can apparently improve the tumor-cytotoxicity activity of the gamma delta T cells and have certain dose dependence. A high-concentration hemsley rockvine root extract can inhibit the growth of tumor cells. The invention initially discovers that a low-concentration hemsley rockvine root extract can notably promote proliferation of the human gamma delta T cells; the low-concentration hemsley rockvine root extract can promote expressions of the porforin, granzyme B and CD107a of the gamma delta T cells; the cytotoxicity activity of the gamma delta T cells is apparently improved; and different extracted components of the hemsley rockvine root are apparently different in proliferation of the gamma delta T cells.

An ultraviolet (UV) disinfection unit for disinfecting catheter line connections is provided. The unit can be used to disinfect solution set and transfer set catheters used for peritoneal dialysis. The unit can comprise a concavely curved bottom surface. A tubing trough of the unit can allow for ambidextrous positioning.

A method for the preparation of a polypeptide of interest in authentic form by enzymatic cleavage of fusion proteins using Granzyme B protease (EC 3.4.21.79). There is also provided fusion proteins comprising a polypeptide of interest and a fusion partner, wherein the junction region between the polypeptide of interest and the fusion partner comprises a Granzyme B protease cleavage site adjacent to the polypeptide of interest, and a human Granzyme B protease variant wherein the Cystein residue no. 228 (chymotrypsinogen numbering) is mutated to Phenylalanine.

A fusion protein including granzyme B, a cell penetrating peptide, a cleavage site, and a targeting moiety, a composition for cell membrane penetration comprising the fusion protein, and an anticancer composition comprising the fusion protein.

The invention provides a sequence for expressing targeted double-recombinant apoptosis proteins of liver cancer, which is a DNA sequence for regulating the expression of two apoptosis proteins of Caspase 3 and Granzyme B by using a specific AFP promoter, and has a nucleotide sequence shown as SEQID No:1. The sequence utilizes the function of targeted regulation of an AFP enhancer / promoter transcriptional regulatory element to lead foreign gene to be expressed in liver cancer cells with positive AFP, thus realizing targeted and high-efficiency anti-tumor effect; and the sequence constructs recombinant activated type Caspase-3 molecule, applies the recombinant activated type Caspase-3 to pro-apoptotic effect for target cells, introduces granzyme B, fuses the granzyme B and the recombinant activated type Caspase-3 molecule, and mediates the apoptosis of the target cells. The invention also provides an application in preparing targeted gene drugs for treating the liver caner with the positive AFP.

By adopting gene recombination technology to implement recombination of vascular endothelial growth factor (VEGF)2-5 exon and gran zyme B (GraB) gene and make VEGF2-5 and GraB be connected and formedinto fusion gene by means of a part of elastic connecon, and utilizing the specific combination of VEGF2-5 and VEGFR to guide GraB and make it target-act on the nescent vascular endothelial cell so as to attain the goal of target-resisting angiogenesis. Said invention uses prokaryocyte secretion type expression system to express recombinant VEGF-Gra fusion protein, and uses immobilized metal ion affinity chromatography and gel filtration method to purity the fusion protein, and uses GraB serine proteinase activity test experiment and chick embryo allantoic membrane angiogenesis anther membrane inhibition experiment to determine the bio-activity of recombinant VEGF-GraB fusion protein.

Cell-targeted serine protease constructs are provided. Such constructs can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer). In some aspects, recombinant serine proteases, such as Granzyme B polypeptides, are provided that exhibit improved stability and cell toxicity. Methods and compositions for treating lapatinib or trastuzumab-resistant cancers are also provided.

Proline compounds as Granzyme B inhibitors, compositions that include the compounds, and methods for using the compounds. Methods for treating cutaneous scleroderma, epidermolysis bullosa, radiation dermatitis, alopecia areata, and discoid lupus erythematosus are provided.

The invention belongs to the field of nuclear medicine, and relates to a granzyme B targeting complex, a radiopharmaceutical and a preparation method and application of the granzyme B targeting complex and the radiopharmaceutical. The structure of the granzyme B targeting complex is shown as a formula (I), wherein R is any one of a difunctional chelating group for radionuclide labeling or a derivative thereof. The granzyme B targeting complex provided by the invention can be labeled by radionuclide to prepare a granzyme B targeting radiopharmaceutical; wherein the granzyme B targeting radiopharmaceutical provided by the invention is simple to prepare, and has better pharmacokinetic characteristics and in-vivo metabolism stability compared with other granzyme B targeting drugs; and therefore, the expression level of granzyme B in body can be noninvasively monitored through nuclear medicine imaging.

The invention discloses an application of quercitrin in preparation of a human gamma delta T cell proliferator, and relates to the technical field of medicines. Quercitrin can remarkably promote proliferation of human gamma delta T cells and promote expression of perforin and granzyme B, so that the quercitrin is of certain dose dependency. The gamma delta T cell treated by the quercitrin can promote expression of p-ERK (Extracellular signal-Regulated Kinase)1 / 2 and p-Akt in active form and promote expression of an anti-apoptoasis protein Bcl-2, so that the gamma delta T cell is of certain dose dependency. The invention discovers the novel medical use of quercitrin and provides experimental references to development of tumor immunotherapy medicines.

The invention belongs to the technical field of biology, and discloses an application of a myeloid cell triggering receptor 2 as a novel coronavirus pneumonia diagnosis or treatment target. Through research, TREM-2 is found to be highly expressed in CD4+ and CD8+T cells of peripheral blood of a patient suffering from novel coronavirus pneumonia and is positively correlated with the severity of a disease. The TREM-2 can be used as a marker for novel coronavirus pneumonia diagnosis and prognosis, and a TREM-2-Fc fusion protein (with an action effect of blocking TREM-2 signals) obviously reducesthe levels of cytokines IFN-g, TNF, IL-2 and Granzyme B. TREM-2 expression has significant correlation with severe indexes of aging, lymphocyte count reduction, C-reactive protein and D-dimer increaseproposed by a''novel coronavirus pneumonia diagnosis and treatment scheme''. Intervention of expression of TREM-2 is prompted to be capable of relieving or even be expected to treat novel coronaviruspneumonia.

A novel cell type has been generated that has both Thl characteristics and cytolytic activity. These Thl / killer cells are CD4+ cells purified from peripheral blood and manipulated to have Thl characteristics such as production of IFN-gamma combined with cytolytic activity similar to cytotoxic T-cells (CTL). The CTL activity is targeted toward diseased cells, not normal cells. The cytolytic activity of the Thl / killer cells is mediated by Granzyme B-Perforin mechanism and results in apoptotic death of diseased cells. Methods of producing and using these Thl / killer cells include isolating CD4+ cells from peripheral blood, activating the CD4+ T- cells to form Thl / killer cells and administering these Thl / killer cells with the cytolytic activity to a patient wherein theThl / killer cells are allogeneic to the patient.

The invention discloses a preparation kit and preparation method of a cell group mainly comprising CD4<+>T cells and a Th1 cell subset, a use of the Th1 cell subset in preparation of an anti-tumor cell preparation, and belongs to the field of biotechnology. The preparation method utilizes a CD4 monoclonal antibody and a culture bottle made of polystyrene, polyvinyl chloride or polyethylene to realize preparation of the cell group mainly comprising CD4<+>T cells, and utilizes two cytokine combination to realize preparation of the Th1 cell subset. Through use of the kit and preparation method provided by the invention, high-ratio CD4<+>T cells in a single karyocyte are obtained. The obtained Th1 cell subset has strong immunocompetence, can secrete a large amount of cell granzyme B, perforin, IFN-gamma and TNF-alpha and has substantial anti-tumor activity.

Covalent Granzyme B inhibitors, compositions that include the compounds, and methods for using the compounds. A method for treating cutaneous scleroderma, epidermolysis bullosa, radiation dermatitis, alopecia areata, and discoid lupus erythematosus are provided.

The invention provides a novel target B7S1 (B7 family member 1) for treating liver cancer. The target reduces activity of cytotoxic T lymphocyte in liver cancer. An inhibitor targeting the B7S1 can promote CD107a expression of the surface of CD8+tumor infiltrating lymphocyte and promote expression of Granzyme B, perforin or IFN-gamma, thereby treating or relieving the liver cancer.

Azaindoline compounds as granzyme B inhibitors, compositions that include the compounds, and methods for using the compounds. Methods for treating cutaneous scleroderma, epidermolysis bullosa, radiation dermatitis, alopecia areata, and discoid lupus erythematosus are provided.

The present invention relates to a modified polypeptide with a biological activity to lyse cell walls of bacteria, wherein the polypeptide has no caspase, clostripain, enterokinase, factor Xa, granzyme B, staphylococcus peptidase I (V8 Protease), plasmin, streptopain, bacillolysin and / or thrombin cleavage site. The invention further relates to nucleic acids with a sequence encoding a polypeptide according to the present invention.