77 results about "Calreticulin" patented technology

The present invention relates to pharmaceutical compositions and methods for the prevention and treatment of autoimmune diseases, infectious diseases, neurodegenerative diseases, and primary and metastatic neoplastic diseases. In the practice of the invention, the compositions are employed comprising: (a) a heat shock protein (hsp) or an alpha(2)macroglobulin (alpha2M); (b) a saponin; and, optionally, (c) an antigenic molecule. The antigenic molecule displays the antigenicity of an antigen of: (a) a cell that elicits an autoimmune response; (b) an agent of an infectious disease; (c) a cancerous cell; or (d) a cell or structure associated with a neurodegenerative or amyloid disease. The hsps that can be used in the practice of the invention include but are not limited to hsp70, hsp90, gp96, calreticulin, hsp 110, grp 170, and PDI, alone or in combination with each other. The antigenic molecule can be covalently or noncovalently bound to the hsp or alpha2M, free in solution, and / or covalently bound to the saponin. The compositions of the invention can be administered alone or in combination with the administration of antigen presenting cells sensitized with an hsp- or alpha2M-antigenic molecule complex.

A method of detecting whether a subject is afflicted with or at increased risk of developing liver cancer is carried out by detecting cleavage of a marker in a sample such as a blood sample from the subject. Suitable markers include but are not limited to, calreticulin, calreticulin precursor, protein disulfide isomerase family A member 3 (PDIA3), and cleavage products thereof. The cleavage, or extent of cleavage, can be as compared to that found in a control sample.

The present invention provides methods for efficient and concomitant recovery of multiple chaperone proteins and / or chaperone protein complexes from a limited sample source. Disclosed are methods involving the use of Free Solution Iso-Electric Focusing (FS-IEF) which can enrich samples containing chaperone proteins and / or chaperone protein complexes from a given sample. The chaperone proteins can be, but are not restricted to calreticulin, gp96, hsp86, hsp84, hsp70, hsp60 and hsp40. The invention also provides methods of recovering chaperone protein complexes for the preparation of vaccines containing chaperone complexes.

Nanosecond pulsed electric field (nsPEF) treatments of a tumor are used to cause the tumor to express calreticulin and stimulate an immune response against the tumor and other tumors in a subject. An immune response biomarker can be measured, and further nsPEF treatments can be performed if needed to stimulate or further stimulate the immune response. Cancers that have metastasized may be treated. The treatment can be combined with CD47-blocking antibodies, doxorubicin, CTLA-4-blocking antibodies, and / or PD-1-blocking antibodies. Electrical characteristics of nsPEF treatments can be based on the size, type, and / or strength of tumors and / or a quantity of tumors in the subject.

Nanosecond pulsed electric field (nsPEF) treatments of a tumor are used to cause the tumor to express calreticulin and stimulate an immune response against the tumor and other tumors in a subject. An immune response biomarker can be measured, and further nsPEF treatments can be performed if needed to stimulate or further stimulate the immune response. Cancers that have metastasized may be treated. The treatment can be combined with CD47-blocking antibodies, doxorubicin, CTLA-4-blocking antibodies, and / or PD-1-blocking antibodies. Electrical characteristics of nsPEF treatments can be based on the size, type, and / or strength of tumors and / or a quantity of tumors in the subject.

The present invention provides methods for efficient and concomitant recovery of multiple chaperone proteins and / or chaperone protein complexes from a limited sample source. Disclosed are methods involving the use of Free Solution Iso-Electric Focusing (FS-IEF) which can enrich samples containing chaperone proteins and / or chaperone protein complexes from a given sample. The chaperone proteins can be, but are not restricted to calreticulin, gp96, hsp86, hsp84, hsp70, hsp60 and hsp40. The invention also provides methods of recovering chaperone protein complexes for the preparation of vaccines containing chaperone complexes.

The invention discloses preparation and application of a tumor marker calreticulin detection kit, and belongs to the fields of genetic engineering and clinical diagnosis. A monoclonal antibody and a polyclonal antibody of the CRT (calreticulin) are prepared by recombinant CRT genetic immune BALB / c mice and new Zealand white rabbits; and an ELISA (enzyme-linked immunosorbent assay) kit with high specificity and sensitivity of which the lowest CRT content is 0.3125ng / ml and the detection limit is 40-0.3125ng / ml is built. The collected clinical sample is detected through the prepared ELISA kit; the result shows that CRT in blood serum of a patient with lung cancer is obviously higher than that in normal blood serum; significant statistic difference exists (P is smaller than 0.01); and an experimental method is provided for diagnosis of the clinical patients with lung cancer.

Novel nucleic acid vectors comprising sequences encoding (a) calreticulin or a domain thereof, and (b) an antigen, such as human papillomavirus oncoproteins E7 or E6 in detoxified form, are disclosed, as are methods for using such vectors to induce antigen-specific immune responses and to treat or prevent development of tumors.

Lower eukaryote host cells in which an endogenous or heterologous Ca2+ ATPase is overexpressed are described. Also described are lower eukaryote host cells in which a calreticulin and / or ERp57 protein are overexpressed. These host cells are useful for producing recombinant glycoproteins that have reduced O-glycosylation.

Human papillomavirus (HPV) infection is the etiological factor for cervical cancer. Provided are HPV vaccines that generate a humoral immune response to prevent new infection, as well as cell-mediated immunotherapy to eliminate established infection or HPV-related disease. HPV vaccines include nucleic acid sequences encoding HPV16 early proteins E6 and E7. Additional nucleic acid sequences in the vaccines include sequences encoding calreticulin and / or the HPV16 late protein L2. Methods using these vaccines are provided that result in therapeutic effects.

A transgenic mouse whose genome comprises a transcriptional control region operably linked to a cDNA encoding calreticulin (CRT) is described.

The invention provides an organic AIE photosensitive probe with mitochondrial targeting and a preparation method and application thereof, and belongs to the technical field of antitumor drugs. The organic AIE photosensitive probe with mitochondrial targeting has a structure as shown in the following formula I in the specification. According to the organic AIE photosensitive probe, mitochondrial ROS oxidative stress is triggered, a large amount of calreticulin translocation is induced to be generated, the immunogenicity of tumor cells is effectively improved, and lasting anti-tumor immune response of an organism is triggered. Therefore, the organic AIE photosensitive probe is applied to preparation of drugs for tumor cell immune response or preparation of reagents for triggering the mitochondrial ROS oxidative stress and inducing generation of calreticulin transposition.

Anthracyclines-treated tumor cells are particularly effective in eliciting an anti-cancer immune response, where the rDNA-damaging agents, such as etoposide and mitomycin C do not induce immunogenic cell death. Anthracyclines induce the rapid, pre-apoptotic translocation of calreticulin (CRT) to the cell surface. Blockade or knock down of CRT suppressed the phagocytosis of anthracyclines-treated tumor cells by dendritic cells and abolished their immunogenicity in mammals, such as mice. The anthracyclines-induced CRT translocation was mimicked by inhibition of the protein phosphatase1 / GADD34 complex. Administration of recombinant CRT or inhibitors of protein phosphatase1 / GADD34 restored the immunogenicity of cell death elicited by etoposide and mitomycin C, and enhanced their antitumor effects in vivo. These data identify CRT as a key feature determining anti-cancer immune responses and delineate a possible strategy for immunogenic chemotherapy.

Anthracyclin-treated turn or cells are particularly effective in eliciting an anti-cancer immune response, where the rDNA-damaging agents, such as etoposide and mitomycin C do not induce immunogenic cell death. Anthracyclins induce the rapid, pre-apoptotic translocation of calreticulin (CRT) to the cell surface. Blockade or knock down of CRT suppressed the phagocytosis of anthracyclin-treated tumor cells by dendritic cells and abolished their immunogenicity in mammals, such as mice. The anthracyclin-induced CRT translocation was mimicked by inhibition of the protein phosphatase1 / GADD34 complex. Administration of recombinant CRT or inhibitors of protein phosphatase1 / GADD34 restored the immunogenicity of cell death elicited by etoposide and mitomycin C, and enhanced their antitumor effects in vivo. These data identify CRT as a key feature determining anti-cancer immune responses and delineate a possible strategy for immunogenic chemotherapy.

The invention relates to a calreticulin-soluble programmed death receptor 1 fusion protein, and a preparation method and a purpose thereof. The invention provides a fusion protein CRTdelta-sPD1 of a mice C-zone-partially-amputated calreticulin and soluble programmed death receptor 1 extracellular domain; the fusion protein is subjected to eukaryotic expression, such that a cell line stably expressing CRTdelta-sPD1 is established; and the CRTdelta-sPD1 is secreted out of the cells by using secretory peptide. The CRTdelta-sPD1 fusion protein provided by the invention has activities of combining cell surface PD-L1 and promoting lymphocyte proliferation and killing. Also, the CRTdelta-sPD1 fusion protein can be activated in vivo, and can induce an immune system to perform specific killing against tumors. Therefore, tumor growth is inhibited, and tumor mice survival time is prolonged. The CRTdelta-sPD1 fusion protein can be adopted as a tumor immunotherapy medicine candidate, and can be used for treating diseases such as tumors.

Techniques for treating a tumor and vaccinating against cancer are described. The techniques include treating the tumor by positioning electrodes over an interface between the tumor and non-tumor tissue and applying sub-microsecond pulsed electric fields. The positioning is facilitated by an imaginary contour line of a threshold value of the electric field. In an example, the imaginary contour line is overlaid over images that include the tumor such that the electrodes are properly positioned over the tumor. The techniques also include vaccinating against cancer by passing sub-microsecond pulsed electric fields through tumor cells of a subject sufficient to cause the tumor cells to express calreticulin on surface membranes. The tumor cells are extracted and introduced with the expressed calreticulin into the subject or another subject, thereby providing a vaccination.

We have recently identified (a) ectocalreticulin as the main source of immunogenicity of cancer cell death induced by chemotherapy or radiotherapy, (b) ectoERP57 as critical protein for inducing cell surface exposure of calreticulin, and (c) that ectoERP57 and ectocalreticulin are cotranslocated together to the tumor cell surface by the mediator of the inhibition of PP1 / GADD34 complex. Here, I show the design of a peptide that inhibits the interaction between PP1 and GADD34 complex. These inhibitor peptide (a) induce ectocalreticulin and ectoERP57 in a variety of tumor cell lines by the mediator of the inhibition of the interaction between PP1 and GADD34, (b) increase the phagocytosis of anticancer targeted proapoptotic peptide and chemotherapy-treated tumor cells by dendritic cells, and (c) improve highly the anticancer activity of proapoptotic peptides and chemotherapy by suppressing or reducing the tumor growth in several isogenic mouse models of colon, mammary, and fibrosarcoma tumors and by increasing the lifespan of transgenic adenocarcinoma mouse prostate mice. These results suggest that these targeted peptides combination approach could serve as a new powerful autonomous anticancer therapy.

The invention relates to heterodera avenae Ha-16674 protein, an encoding gene and application thereof. An amino acid sequence of the heterodera avenae Ha-16674 protein is shown as SEQ ID NO: 1, and a cDNA full-length nucleotide sequence of a gene for encoding the heterodera avenae Ha-16674 protein is shown as SEQ ID NO: 2. Experiments show that the Ha-16674 and Bax can inhibit blade cell death caused by the Bax when being jointly injected into tobacco leaves. Full-length overexpression of the Ha-16674 gene in arabidopsis thaliana can obtain stable genetic T3 generation transgene positive plants, and calprotectin Ha-16674 in heterodera avenae can reduce immune defence reaction of the arabidopsis thaliana to promote pesudomona syringae infection. The heterodera avenae Ha-16674 protein disclosed by the invention provides a new target Ha-16674 for nematode-resistance plant culture and has good theoretical guidance significance on culturing broad-spectrum heterodera-resistance crops.

The present invention provides a method that allows highly efficient and highly reliable evaluation of genomic stability of pluripotent stem cells, a method for removing pluripotent stem cells that have been identified as genomically unstable by the evaluation method from a culture of pluripotent stem cells to be evaluated, and a synthetic peptide that can be used for the methods. The methods provided by the present invention include preparing a culture of pluripotent stem cells of interest and analyzing an expression level of calreticulin for the pluripotent stem cells in the culture followed by identifying genomic stability or genomic instability of the stem cells on the basis of the expression level of calreticulin.

This invention relates to a method for detecting urothelial carcinoma using an antibody that specifically reacts with a calreticulin protein or a fragment thereof and immunoassaying a calreticulin protein in a sample.

The invention discloses an activated state resisting T cell antibody vaccine for preventing and / or treating immune-related diseases. The active component of the activated state resisting T cell antibody vaccine is a polyclonal antibody or a monoclonal antibody of an activated state resisting T lymphocyte cell and / or at least one of the following proteins or polypeptides: 1) a polypeptide which is obtained by losing a calreticulin protein and at least contains amino acid residues from the 21st to the 253th on the tail end of an amino acid of GenBank Accession Number AAH03453; 2) a polypeptide which is obtained by losing a ERp57 protein and at least contains the amino acid residues from the 27th to the 250th on the tail end of an amino acid of GenBank Accession Number P27773; 3) a vimentin protein; 4) the calreticulin protein; and 5) the ERp57 protein. The vaccine can be used for preventing and / or treating immune-related diseases of diabetes I, and / or systemic lupus erythematosus, and / or multiple sclerosis, and / or chronic hepatitis B, and / or rheumatoid arthritis, and / or experimental encephalomyelitis, and / or hypersensitivity diseases and the like.

The present invention relates to a method for determining the susceptibility of a patient tumor cell to a cancer treatment, which method comprises the detection or measure of CRT, KDEL receptor and / or ERp57 on the surface of a tumor cell.

The present application is directed to plants with improved properties where the expression of calreticulin, BET1-like polypeptides, DUS1-like polypeptides, ES43-like polypeptides, H0N5-like polypeptides or GSA1 polypeptides are modified. The improved property can be enhanced yield.

The present invention relates to a method for determining the susceptibility of a patient tumour cell to a cancer treatment, which method comprises the detection or measure of CRT, KDEL receptor and / or ERp57 on the surface of a tumour cell.

The invention discloses a detecting method and its agent box and gene chip of tyr-ser-leu protein anti-hepatocarcinoma effect, which comprises the following steps: detecting the changing condidtions of gene NDUFA2, NDUFA10, NDUFS1, SUCLG1, Calreticulin, PTEN, Akt1, Akt2, P21and P27 expression level in the biological material after acted by tyr-ser-leu protein; displaying downward for gene NDUFA2, NDUFA10,NDUFS1,SUCLG1,Akt1,Akt2 and upward for the expression level of gene Calreticulin,PTEN, P21,P27; possessing anti-hepatocarcinoma effect. The invention provides a rapid detecting path of tyr-ser-leu protein anti-hepatocarcinoma effect on the molecular level.

The invention discloses a diagnostic marker and equipment for detecting the autism spectrum disorders (ASD), and application. The diagnostic marker is one protein combination group that is formed by any three or more than three kinds of proteins including alpha-1-antitrypsin, calmodulin, calreticulin, complement protein C3, integrin alpha-Iib, thrombospondin-1, and vitronectin. According to the invention, the plasma and peripheral blood mononuclear cells protein marker that are used for ASD diagnosis are determined; and the ASD is diagnosed by detecting the expressions of the marker protein inthe plasma and the protein simultaneously, so that the objectivity, specificity and accuracy of diagnosis are enhanced; and since a few of protein types are detected, the detection efficiency is improved.

Therapeutic and cosmetic uses and applications of calreticulin are provided. In particular, the invention relates to therapeutic and cosmetic uses and applications of calreticulin to a patient in need of such treatment including in tissue repair, wound healing, ulcers, reducing scar formation, and reducing or eliminating wrinkles.

The invention discloses a wheat calreticulin fragment TaCRT1-206. The wheat calreticulin fragment TaCRT1-206 is a protein having an amino acid sequence represented by SEQ ID NO:2 in a sequence table, or is a protein having an amino acid sequence derived from the SEQ ID NO:2, having activities same with the amino acid residue sequence of the SEQ ID NO:2 and having an amino acid radical sequence concretely obtained through substituting, deleting or adding above one amino acid residual radicals to the amino acid residue sequence of the SEQ ID NO.2. The invention also discloses an application of a coding sequence TaCRT1-681 of the wheat calreticulin fragment TaCRT1-206. The transfer of the wheat calreticulin fragment TaCRT1-206 to plants through a genetic engineering method can improve the salt resistances of the plants. The above gene is an endogenous gene existing in the grain crop wheat, so the excess expression of the gene does not influence of the food safety of the plants, and the gene can be widely applied to the breeding of a plurality of plants.