35 results about "Calreticulin" patented technology

To provide multifunctional molecules that bind to calreticulin and uses thereof.SOLUTION: Multifunctional molecules that include i) an antigen binding domain that binds to a calreticulin protein; and one, two or all of: (ii) an immune cell engager (e.g., chosen from an NK cell engager, a T cell engager, a B cell engager, a dendritic cell engager, or a macrophage cell engager); (iii) a cytokine molecule; and / or (iv) a stromal modifying moiety are disclosed. Additionally disclosed are nucleic acids encoding the same, methods of producing the aforesaid molecules, and methods of treating a cancer using the aforesaid molecules.SELECTED DRAWING: None

The present disclosure relates to antibodies, and antigen-binding fragments thereof, that bind to mutant calreticulin. The present disclosure also relates to bispecific antibodies, and bispecific antigen-binding fragments thereof, that bind to mutant calreticulin and cluster of differentiation 3. Also provided are cells expressing the antibodies, polynucleotides and vectors expressing all of some of the antibodies, pharmaceutical compositions comprising the antibodies, and methods of inhibiting the growth or proliferation, or treating, myeloproliferative neoplasm.

The invention discloses a method for extracting calreticulin from tissues and application. The tissue cell extract extracted by the method contains calreticulin and can be used for preparing drugs or vaccines for preventing cancers. Experimental results show that after the tissue cell extract is immunized for several weeks, specific immune response of an organism can be triggered, cancerous cells in the organism can be removed, and therefore the aim of preventing cancers is achieved. The tissue cell extract provided by the invention can be used as a tumor preventive vaccine for preventing autologous or allogenic tumors and reducing the incidence rate of cancers in healthy people.

The invention belongs to the technical field of tumor vaccines, and relates to a cell membrane-derived tumor vaccine with a dendritic cell regulation function and application thereof. The tumor vaccine comprises a tumor cell membrane shell which is subjected to induction treatment to generate immunogenic death, and a cationic carrier core which entraps small interfering RNA (siRNA) and an immunologic adjuvant. According to the preparation method disclosed by the invention, a tumor cell membrane of calreticulin eversion is obtained in a drug induction manner, so that the immunogenicity of the tumor vaccine is improved, and the uptake ability of the dendritic cells to the tumor vaccine is improved; meanwhile, the cation core loaded with siRNA can down-regulate up-regulated negative feedback regulatory factors after the dendritic cells are activated by antigens, inhibit a negative feedback pathway for immunoregulation of the dendritic cells, and enhance the in-vivo immune activation effect of the tumor vaccine.

The invention relates to the technical field of gene engineering, in particular to a novel calreticulin-carrying oncolytic adenovirus as well as application and a preparation method thereof. In the oncolytic adenovirus, a plasmid skeleton of a recombinant plasmid is type-5 adenovirus, and a nucleotide sequence of an E3 region of the plasmid skeleton has Gp19k fragment deletion; the recombinant plasmid comprises a CMV promoter and a nucleotide sequence used for coding calreticulin, the CMV promoter and the nucleotide sequence used for coding calreticulin are located at the deletion position of a Gp19k fragment, and the CMV promoter and the nucleotide sequence used for coding calreticulin are introduced into the deletion position of the Gp19k fragment of the type 5 adenovirus. The oncolytic virus can be normally replicated, calreticulin overexpression is realized under the condition that the virus activity is ensured, and the method has a good effect on various cancer cells, and can become an effective means for a'general cancer species' therapy.

Nucleic acids encoding recombinant fusion proteins directed to calreticulin are described, as well as pharmaceutical compositions comprising such nucleic acids and therapeutic methods using such nucleic acids and pharmaceutical compositions, such as for treating cancer.

The present invention relates generally to methods for preventing and / or treating myeloproliferative disorders. More specifically, the myeloproliferative disorders are those associated with the presence of a frameshift mutation in the calreticulin (CALR) gene of a cell involved in the myeloproliferative disorders. The present invention also relates to immunological agents, such as antibodies, to calreticulin, methods for preventing and / or treating myeloproliferative diseases using the immunological agents, and chimeric antigen receptors having extracellular domains based on antibodies to calreticulin.

Provided are a use of recombinant calreticulin in hair growth, hair breeding, hair protection or anti-hair loss and a related product. The recombinant protein is derived from the full length of calreticulin or a fragment thereof, and has the functions of treating hair loss and improving hair by means of injection or application. Therefore, calreticulin is expected to be developed into an effective method and means for treating hair loss and improving hair.

Provided are nanobodies that bind human calreticulin, fusion proteins including the nanobodies, pharmaceutical compositions including the nanobodies or fusion proteins, and radioconjugates of the nanobodies or fusion proteins.

A diagnostic, preventive, or therapeutic agent may be used for a myeloproliferative neoplasm. An antibody or a functional fragment thereof that binds to a cleaved mutant CALR protein, may include an antigen-recognition site in (a) a polypeptide chain having an amino acid sequence set forth in SEQ ID NO: 1 or (b) a polypeptide chain having an amino acid sequence having deletion, substitution, or addition of one to several amino acids in SEQ ID NO: 1; and a diagnostic, preventive, or therapeutic agent for a myeloproliferative neoplasm containing the antibody.

The present disclosure provides polymeric matrices comprising calreticulin (CRbT) and methods of producing and using such matrices. The polymeric matrices are useful in treatment of wounds (e.g., chronic diabetic wound).

The present invention provides a mitochondrion-targeted fenofibric acid, and the mitochondrion-targeted fenofibric acid is a triphenylphosphine fenofibric acid conjugate. A method for constructing the mitochondrion-targeted fenofibric acid is to synthesize the mitochondrion-targeted fenofibric acid by coupling aminotriphenylphosphine with fenofibric acid. The specific steps include: dissolving fenofibric acid in dichloromethane containing triethylamine; then adding aminotriphenylphosphine, 1-hydroxybenzotriazole and EDCI to obtain a mixture; washing and rotary evaporation to obtain the mitochondrion-targeted fenofibric acid. The mitochondrion-targeted fenofibric acid of the present invention can efficiently inhibit respiratory chain complex I and generate a large amount of mtROS. Its cytotoxic effect is nearly 10 times that of fenofibrate, and it shows specific killing of tumor cells. The mitochondrion-targeted fenofibric acid can also cause calreticulin membrane translocation and IFN-I secretion, induce an in-situ tumor vaccine effect, and synergistically treat tumors with immune checkpoint blockade therapy.

The invention discloses a composition for treating the problem of skin decline, a preparation method and application, and belongs to the technical field of health care and skincare, and the composition is mainly prepared from the following raw materials: cactus flower extract, abalone peptide, melibiose and the like. After the cactus flower extract, the melibiose and the abalone peptide are combined, the postpartum anti-aging effect is achieved through a new mechanism, and the anti-aging effect is obviously improved and is superior to that of any single component. Experimental research proves that the composition has anti-aging activity by activating calreticulin of fibroblasts in postpartum skin, enhancing the antigen presentation capacity of dendritic cells, activating a non-classical NF-kappa B signal channel, promoting lymphocyte homing and prolonging T cell telomere, does not have the mechanism when any component is independently used, and has no toxic or side effect. The composition is innovative in the anti-aging aspect.

The invention relates to an isolated chimeric antigen receptor (CAR) comprising an antibody or antigen binding portion thereof that specifically binds to mutant calreticulin. Disclosed are CAR-T cells for use in the treatment of a myeloid malignancy, methods for their production, and their use.

Therapeutic and diagnostic methods are provided, which methods relate to the induction of expression of calreticulin on phagocytic cells. Specifically, the methods relate to macrophage-mediated programmed cell removal (PrCR), the methods comprising increasing PrCR by contacting a phagocytic cell with a toll-like receptor (TLR) agonist; or down-regulating PrCR by contacting a phagocytic cell with an inhibitor of Bruton's tyrosine kinase (BTK). In some embodiments, an activator of TLR signaling or a BTK agonist is provided in combination with CD47 blockade.

Anti-mutant calreticulin (mutCALR) antibody-drug conjugates comprising pyrrolobenzodiazepine dimers are disclosed. Also disclosed are related kits, and pharmaceutical compositions. Methods of treating myeloproliferative neoplasms with the anti-mutCALR antibody-drug conjugates are also disclosed.

Provided are a corn peptide having an anti-tumor effect, and a preparation method therefor and a use thereof. The corn peptide can obviously eliminate reactive oxygen species in tumor cells, increase the concentration of free calcium ions in the cytoplasm of the tumor cells and reduce the mitochondrial membrane potential of the tumor cells, and also can enhance the expression levels of mRNA and proteins of an IP3R and calreticulin, and further affect the calcium homeostasis of the tumor cells. In addition, the corn peptide can up-regulate the expression of tumor suppressor genes PTEN, P21 and P27, down-regulate the expression of a cell proliferation marker PCNA and a tumor-promoting gene Akt, and mediate an anti-tumor effect by means of PTEN and Akt cell signaling pathways.

The invention discloses a tumor cell vaccine, a preparation method thereof and application of the tumor cell vaccine in preparation of diffuse large B-cell lymphoma immunotherapy drugs. Research finds that after a cell culture medium is subjected to arginine deprivation treatment, DLBCL cell proliferation is remarkably inhibited, ICD (immunogenic cell death) is induced, and ICD key markers including calreticulin (CALR) membrane ectropion, high mobility group protein B1 (HMGB1) and ATP are released. These molecules activate dendritic cells and CD8 + T cells, enhancing antigen presentation and immune response. Further zoology experiment results show that the whole-cell vaccine subjected to arginine deprivation treatment shows a good anti-tumor effect in a mouse model.

The problem addressed by the present invention is to produce a novel antibody recognizing a mutant CALR protein at a site distinct from the sites recognized by conventional antibodies, and to provide pharmaceuticals using the same. The present invention provides a composition for treating a tumor, the composition comprising an antibody or an antigen-binding fragment thereof that binds to a region N-terminal to a mutation site in a mutant calreticulin and binds to the mutant calreticulin present on the cell surface. The present invention also provides a method for producing an antibody that binds to a region N-terminal to a mutation site in a mutant calreticulin, said method comprising a step for screening: an antibody that binds to the mutant calreticulin present on a cell surface; or an antibody that binds to a dimer of the mutant calreticulin.

The invention relates to peptidomimetic inhibitors of calreticulin, to their prodrugs and to pharmaceutical compositions comprising them. Specifically provided are cyclic peptidomimetic s and their prodrugs having a lipophilic charge mask, thus metabolically stable and highly bioavailable. Methods for treatment of autoimmune diseases and other conditions associated with calreticulin are also provided.

The present disclosure relates to binding domains that bind Calreticulin (CALR) and binding domain that binds to CD3, as well as binding moieties comprising such binding domains. The present disclosure further relates to the use of such binding domains or binding moieties in the treatment of cancer. The present disclosure also relates to nucleic acid encoding such binding domains or binding moieties, and a vector and cell comprising such nucleic acid.

The present disclosure relates to antibodies, and antigen-binding fragments thereof, that bind to mutant calreticulin. The present disclosure also relates to bispecific antibodies, and bispecific antigen-binding fragments thereof, that bind to mutant calreticulin and cluster of differentiation 3. Also provided are cells expressing the antibodies, polynucleotides and vectors expressing all of some of the antibodies, pharmaceutical compositions comprising the antibodies, and methods of inhibiting the growth or proliferation, or treating, myeloproliferative neoplasm.

The present invention relates to a novel fusion protein in which a monobody specifically bidning to a tumor antigen is linked to L-asparaginase for treating solid cancer more efficiently, and a use thereof, paticularly to a novel fusion protein comprising a recombinant monobody which specifically binds to clareticulin and an L-asparaginase linked to the C-terminus of the recombinant monobody, wherein the recombinant monobody has a peptide that specifically binds to the calreticulin inserted into at least one of the BC loop and the FG loop of human fibronectin domain III (Fn3) as an asparaginase-based novel anticancer agent targeting tumor antigen whose drug delivery efficacy to tumor tissue is enhanced.

The presently claimed and described technology provides vaccine compositions comprising at least two mutant-calreticulin (CALR)-peptides, wherein the at least two peptides have overlapping sequences and methods for administration of the vaccine compositions to induce or elicit an antitumor response or improve or enhance antitumor T cell immunity and methods of preventing, treating, reducing, or slowing progression or development of a hematological malignancy in a subject with a calreticulin mutation.

Methods of inhibiting the growth or proliferation, or treating, myeloproliferative neoplasm using bi-specific molecules that bind to mutant calreticulin and CD3 are described.

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a calreticulin ectropion tumor cell membrane wrapped drug-loaded peptidoglycan as well as a preparation method and application of the calreticulin ectropion tumor cell membrane wrapped drug-loaded peptidoglycan. According to the invention, the complete peptidoglycan (WPG) is extracted from bacteria, so that the complete peptidoglycan (WPG) is used as a composite immunologic adjuvant, namely, the complete peptidoglycan (WPG) is used as a carrier and has an inherent immune activation capability. According to the invention, a CRT extroversion CT-26 tumor cell model is constructed, and the cell membrane of the CRT extroversion CT-26 tumor cell model is extracted to coat the surface of the drug-loaded peptidoglycan, so that the uptake of the dendritic cells to the whole particle system and the lymph node drainage capability are effectively improved; animal in-vitro experiments verify the immunotherapy effect of the drug-loaded peptidoglycan treatment system and the combined treatment effect of the drug-loaded peptidoglycan treatment system combined with radiotherapy. The invention provides a safe and efficient immunotherapy drug, and provides a new scheme for realizing effective cancer immunotherapy and combined therapy.

The present disclosure relates to antibodies and antigen-binding fragments thereof that bind to a mutant calreticulin. The disclosure also relates to bispecific antibodies and bispecific antigen-binding fragments thereof that bind to mutant calreticulin and cluster of differentiation 3. Also provided are cells expressing the antibodies, polynucleotides and vectors expressing all of some of the antibodies, pharmaceutical compositions comprising the antibodies, and methods of inhibiting the growth or proliferation of or treating myeloproliferative tumors.

The invention discloses application of a composition containing a CDK2 inhibitor and an anti-PD-1 antibody in preparation of antitumor drugs, and relates to the technical field of biological medicines, and the composition comprises the CDK2 inhibitor, the anti-PD-1 antibody and an anthracycline chemotherapeutic drug. According to the application of the composition containing the CDK2 inhibitor and the anti-PD-1 antibody in preparation of anti-malignant tumor drugs, the CDK2 inhibitor enhances ICD induced by anthracycline drugs and CDK2 inhibition of up-regulation interferon stimulating genes ISGs and promotes infiltration of T cells and dendritic cells (DCs) by inhibiting activity of tumor cells CDK2 and promoting apoptosis stress, calreticulin (CRT) exposure, HMGB1 release and ATP secretion.

The present application provides methods for the treatment of clonal hematopoietic disorders using compounds that modulate kinase activity or antibodies that binds to human mutant calreticulin (CALR).

A pharmaceutical which exhibits sufficient anticancer effects by using an antibody which binds to a mutant CALR protein and another anticancer agent in combination. A pharmaceutical for preventing and / or treating a cancer, including an antibody which specifically binds to a mutant calreticulin protein or a functional fragment thereof and a drug selected from the group consisting of an alkylating agent, a platinum preparation, an antimetabolite, a ribonucleotide reductase inhibitor, a nucleotide analog, a topoisomerase inhibitor, a microtubule polymerization inhibitor, an antitumor antibiotic, an interferon, a cytokine preparation, a molecular targeting drug, a nucleic acid synthesis inhibitor, a jak inhibitor, and a cancer immunotherapeutic agent in combination.