121results about "P53 protein" patented technology

Provided are compounds that may bind a target protein, and result in modification of the target protein. The compounds may further bind a modifier protein. The modifier protein may carry out or enhance the modification of the target protein. The modification may activate or reactivate the target protein. Also provided are methods of using the compounds.

The invention discloses PROTAC capable of efficiently degrading a target protein and a preparation and delivery method of the PROTAC, a phase separation sequence and a designed double-targeting molecule are fused to respectively target the target protein and a proteasome, and phase separation of the PROTAC and the target protein is realized, so that efficient degradation of the target protein is realized. In addition, the delivery of PROTAC is also realized by encapsulating mRNA with LNP, and the target protein can also be efficiently degraded in cells, so that a way is also provided for the delivery of peptide or protein PROTAC into the human body.

The invention relates to the technical field of gene engineering, and particularly discloses application of a gene recombinant of an adenovirus vector and a p53 gene, and application of the recombinant constructed by utilizing the adenovirus vector and the human p35 gene in preparation of drugs for treating proliferative diseases. The recombinant adenovirus is packaged by adopting an AdMax packaging system framework, the E1 / E2-deleted replication-deficient adenovirus is obtained through intracellular homologous recombination, recombinant virus particles with relatively high titer can be obtained, and the recombinant virus particles can have relatively high expression in cells with proliferative diseases, so that the recombinant adenovirus can be used for treating proliferative diseases. By means of the method, in-vivo transfer of the exogenous p53 gene and efficient expression of the exogenous p53 gene in hyperplasia tissue of a patient are achieved, so that the purpose of treatment is achieved, and gene treatment of hyperplasia diseases is achieved.

Provided herein are methods of treating or preventing cancer in a subject in need thereof, the methods comprise administering to the subject in need thereof (a) one or more nucleic acids encoding an elephant p53 protein, an elephant LIF protein, and / or combinations thereof, or (b) one or more elephant p53 proteins, elephant LIF proteins, and / or combinations thereof. Also provided are pharmaceutical compositions comprising a pharmaceutically acceptable carrier and (a) one or more nucleic acids encoding an elephant p53 protein, an elephant LIF protein, and / or combinations thereof, or (b) one or more elephant p53 proteins, elephant LIF proteins, and / or combinations thereof.

Disclosed are methods of isolating T cells having antigenic specificity for a mutated p53 amino acid sequence encoded by a cancer-specific p53 mutation, the method comprising: inducing autologous APCs of the patient to present the mutated p53 amino acid sequence; co-culturing autologous T cells of the patient with the autologous APCs that present the mutated p53 amino acid sequence; and selecting the autologous T cells. Also disclosed are related methods of preparing a population of cells, populations of cells, pharmaceutical compositions, and methods of treating or preventing cancer.

The present invention is in the field of oncology, and more particularly of cancer stem cells. It relates to a method for producing cancer stem cells based on overexpression of Δ133p53β isoform, Δ133p53γ isoform, or both Δ133p53β and Δ133p53γ isoforms; a method for predicting the risk that treatment with a chemotherapeutic anti-cancer agent induces cancer stem cells in a subject suffering from cancer from a cancer sample of said subject, based on detection of an increase in Δ133p53β isoform, Δ133p53γ isoform, or both Δ133p53β and Δ133p53γ isoforms following chemotherapeutic anti-cancer treatment; to therapeutic uses of a combination of chemotherapeutic anti-cancer agent and an agent reducing Δ133p53β isoform, Δ133p53γ isoform, or both Δ133p53β and Δ133p53γ isoforms expression; and also to screening methods for anti-cancer stem cells agents.

Disclosed is an isolated or purified T cell receptor (TCR) having antigenic specificity for mutated human p53. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

Mutations in oncogenes and tumor suppressor factors contribute to the development and progression of cancer. This disclosure describes compounds and methods for restoring DNA-binding affinity of p53 mutants, as well as their use in diagnostic assays to guide the treatment of subjects with said compounds for cancer. The compounds of this disclosure can bind to mutant p53 and restore the ability of p53 mutants to bind to DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers containing p53 mutations.

Provided herein are methods and compositions for treating cancer in an individual comprising administering to the individual an effective amount of at least one CD122 / CD132 agonist, at least one immune checkpoint inhibitor and a viral composition comprising one or more viruses engineered to overexpress a tumor suppressor gene and / or an adenoviral death protein. Also provided herein are methods and compositions for treating cancer in an individual comprising administering to the individual an effective amount of at least one oncolytic viral composition and at least one CD122 / CD132 agonist and at least one immune checkpoint inhibitor. Also provided herein are methods of enhancing anti-tumor efficacy by administering the agents described above in combination with other cancer therapies. In highly aggressive forms of cancer, known to be generally resistant to immune therapies, these treatments unexpectedly resulted in complete tumor remissions and curative outcomes.

The invention provides a p53 fusion protein based on a targeted colorectal cancer marker CEA and application of the p53 fusion protein in preparation of medicines for inhibiting colorectal cancer, and relates to the field of biological medicines. The fusion protein comprises any one of the following components: p28-p53, MBP-TEV-p14ARF (1-63)-linker-p28, p28-p53-CEABP1, CEABP1-p28-p53, and CEABP2-p28-p53, and the fusion protein comprises any one component selected from the group consisting of the following components: a protein A, a protein B, a protein A, a protein B, a protein C and a protein B, according to the application, p53 and p14 ARF proteins for inhibiting cell proliferation in a human body, cell-penetrating peptide and designed protein CEABP1 or CEABP2 of a targeted binding colorectal cancer marker CEA are fused for the first time, and cell experiments and mouse experiments prove that the protein has a relatively high function of inhibiting growth of colorectal cancer cells, does not influence normal cell growth and has a wide application value.

An isolated or purified T cell receptor (TCR) having antigen specificity for human p53Y220C or human p53R175H is disclosed. Related polypeptides and proteins as well as related nucleic acids, recombinant expression vectors, host cells, populations of host cells and pharmaceutical compositions are also provided. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.

The present disclosure belongs to the field of biotechnology, and specifically relates to a preparation method for an adenovirus p53 (Ad-p53)-loaded dendritic cell (DC) vaccine. The present disclosure includes steps of peripheral blood collection and peripheral blood mononuclear cell (PBMC) separation, PBMC sorting, DC activation, Ad-P53-transfected DC and DC vaccine preparation. P53 can be expressed on a surface of DC as a tumor-associated antigen (TAA) through DC purification, specific multiplicity of infection (MOI) and infection modes, and the Ad-P53-transfected DC has obvious antigen presentation effect, which can be used as a vaccine to activate T cells to kill tumors.

Compounds comprising an albumin-binding domain and a mutant or wild-type p53 peptide, as well as pharmaceutically acceptable salts thereof, are disclosed herein. Furthermore, methods for inducing an immune response in a subject, and methods for inducing an immune response in a subject by administering such compounds, are disclosed herein.

We provide cultured cell sheets. [Solution] A cultured cell sheet is provided, which is made from cells collected from nasal mucosal tissue, and contains 50-90% undifferentiated cells relative to the total number of cells, wherein, in one embodiment, the undifferentiated cells are positive for p63, and the cultured cell sheet is a mixture of nasal mucosal epithelial cells and nasal mucosal epithelial stem cells or nasal mucosal epithelial progenitor cells, as well as one or more of the following cells: other epithelial cells or other epithelial stem cells, mesenchymal stem cells, fibroblasts, vascular endothelial cells, vascular endothelial progenitor cells, and adipocytes. [Effects] The cultured cell sheet of the present invention engrafts on areas of mucosal tissue defects such as inflammation and granulation tissue formation on the surface of bone tissue in the middle ear, promoting the regeneration of mucosal tissue, including mucosal tissue covering bone tissue, efficiently suppressing inflammation occurring in the bone tissue of the middle ear, and inhibiting characteristic fibrosis, granulation tissue formation, and poor epithelial formation that occur during bone tissue inflammation.

Disclosed herein are polypeptide fragments and polynucleotides based on mutant capicua transcriptional repressor (CIC), catenin beta 1 (CTNNB1), v-erb-b2 erythroblastic leukemia viral oncogene homolog B (ERBB2), kirsten rat sarcoma (KRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), phosphatase and tensin homolog (PTEN), splicing factor 3b subunit 1 (SF3B1), SRY-box transcription factor 17 (SOX17), tumor protein 53 (TP53), and cytomegalovirus (CMV) sequences, vectors, host cells, viruses, methods for generating CD8+ T-cells, and methods of treatment. Also disclosed herein are T-cell receptors (TCRs), polynucleotides, vectors and cells comprising the TCRs, and methods of treatment.

Disclosed is an isolated or purified T cell receptor (TCR) having antigenic specificity for mutated human p53. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

The invention belongs to the field of biological medicine, and particularly relates to an engineered macrophage, an exosome, an engineered macrophage exosome delivery system and application thereof. The engineering macrophage is constructed by transfecting the PDCD1 gene and the Trp53 gene into the macrophage, and then the engineering macrophage is injected into the abdominal cavity of a mouse with colon cancer. The engineered macrophage continuously secretes exosomes containing expression products of the PDCD1 gene and the Trp53 gene in the abdominal cavity of a mouse and directly acts on colon cancer cells. Experiments show that the engineered macrophage has good killing ability and targeting ability, and can effectively inhibit tumor growth.

An object of the present invention is to provide a cultured cell sheet that can solve problems accompanied by defects of mucosal tissue as described above, such as inflammation in mucosal tissues covering bone tissues and granulation tissue formation. In order to solve the problems described above, the present inventors have conducted research and development with examinations from various angles. As a result, it has been found that a cultured cell sheet obtained by culturing cells collected from a nasal mucosal tissue as a source under specific conditions, and reconstructing the cells into a sheet are engrafted onto mucosal tissue defective sites, such as due to inflammation on the surface of middle ear bone tissues and granulation tissue formation; promote the regeneration of mucosal tissues, such as those covering bone tissues; efficiently reduce inflammation that occurs in a middle ear bone tissue; and prevent fibrosis, granulation tissue formation, defective epithelial formation, and the like that are characteristic of bone tissue inflammation, thereby demonstrating that the cultured cell sheet can solve the above-described problems. It is also found that a cultured cell sheet made from cells collected from a nasal mucosal tissue of the present invention is also useful for preventing inflammation of bone tissues in other areas of the body other than the middle ear.

Provided herein are systems, methods, and compositions for a Remote-Controlled Alteration / Induction of Cellular Apoptosis. In one embodiment, the method comprises radio- controlled mRNA therapy to treat cancer.

Formulations are disclosed that include SADA complexes. The formulations provide sufficient shelf life without excessive degradation or multimerization of the SADA complexes. Use of the formulations to treat cancer is further disclosed.

Provided are methods for inserting a large gene / polynucleotide between about 4.5Kb and about 8Kb and lacking a selection marker into a target genomic position in a cell by delivering the gene / polynucleotide by two AAV vectors in the presence of a p53-binding protein 1 (53BP1) inhibitor and a DNA-dependent protein kinase catalytic subunit (DNA- PKcs) inhibitor. The disclosed methods improve large gene insertion by at least 10-fold and obviate the need for a selection marker in the vector design, thereby providing more room in the AAV vector for gene delivery.

Methods for inducing basal cell carcinoma (BCC) or BCC tumors, as well as an inducible non-human animal models of BCC, are defined herein. The methods and animal models comprise targeting Ptch1 and / or a tumor suppressor gene via conditional expression of one or more short hairpin RNAs (shRNAs) in the skin of said animals.

Some embodiments of the present disclosure relate to one or more compositions that upregulate the production of one or more sequences of mRNA. The sequences of mRNA may encode for translation of a target biomolecule, thereby causing an increase in bioavailability of the target biomolecule within a subject that is administered the one or more compositions. In some embodiments of the present disclosure, the target biomolecule is a protein, such as p53.

The present invention relates to compositions and methods employing conjugates that include a self-assembly and disassembly (SADA) polypeptide and a binding domain. The present invention encompasses the recognition that conjugates with a SADA polypeptide have certain improved biological properties. SADA-conjugates are described, along with uses thereof (e.g., as therapeutic or diagnostic agents) and methods of manufacture.

The invention is based on in vitro transcribed or in vitro synthesized RNA compounds for a translation of tumor suppressor proteins in subjects suffering from a proliferative disease such as cancer. The invention provides the RNA compounds, as well as compositions for their delivery or administration to subjects

A method of obtaining cell derived vesicles comprising an active wild-type p53 is disclosed. The method comprising: (i) isolating cell derived vesicles from a biological sample comprising cells; and (ii) treating the cell derived vesicles with a DNA damaging agent, or the method comprising: (i) treating cells with a DNA damaging agent; and (ii) isolating cell derived vesicles from a biological sample comprising the cells. A proteinaceous preparation comprising cell derived vesicles and a pharmaceutical composition comprising the proteinaceous preparation are also disclosed. Methods of treating a disease, disorder or condition associated with a mutant or a nonfunctional p53 protein and methods of inducing apoptosis of a target cell comprising a mutant or a nonfunctional p53 protein are also disclosed.

The application relates to the field of nanobiomedicine, and particularly relates to an engineered vesicle and a preparation method and application thereof. The engineered vesicle comprises a nano-vesicle and a calcium phosphate mineralized film coated on the surface of the nano-vesicle, and the nano-vesicle contains p53 protein. The p53 protein contained in the engineered vesicle promotes tumor aging to inhibit proliferation and metastasis, and the aged tumor cells can enhance the immune response against tumors at the tumor site, and the outer calcium phosphate mineralized film coating enables the nano-vesicle particles to effectively reduce the risk of severe inflammation in the body, to be gathered at the tumor site by the EPR effect, and under the acidic tumor microenvironment, the pH-sensitive calcium phosphate mineralized film is broken to expose the vesicle with certain immune stimulating capacity, which synergistically activates the immune response against tumors. The engineered vesicle has wide application prospects, and also lays a foundation for the design and development of a corresponding drug delivery system.

The present disclosure generally relates to cancer therapies and, in some embodiments, to using genetic circuits designed for targeted cancer therapies. The genetic circuit, in some embodiments, utilizes a suitable vector capable of delivering DNA sequences comprising functional units comprising a transcriptional promoter, target sequences and a transcriptional terminator. Together, the genetic circuit, in some embodiments, may trigger apoptosis — a target protein activity where cell death occurs — in cancer cells, and protect non-cancer cells from apoptosis. In some embodiments, the genetic circuit may direct target protein activity in cancer cells, while not directing protein activity in non-cancer cells. However, in the presence of certain stimuli, the inhibition is relieved, which may lead to the induction of target protein activity in cancer cells. In addition, some embodiments are generally directed to vectors comprising a first sequence encoding at least a portion of Mdm2 and a promoter, and a second sequence encoding a promoter and a fusion protein comprising at least a portion of p53 and iCasp-9 (or another protein capable of achieving a therapeutic objective), optionally connected by a linker sequence capable of allowing each protein subunit of the fusion protein to be independently active but subject to the same proteolytic pathways as p53 in cancer and non-cancer cells. Other aspects are generally directed to methods of making or using such compositions, kits including such compositions, or the like.

Embodiments of the disclosure concern methods and compositions related to T cell receptors directed against breast cancer neoantigens, including immunotherapeutic compositions of any kind. In specific embodiments, the TCRs are identified following particular methods of producing neoantigen-specific T cells, including particular culturing methods.

Disclosed herein are compounds comprising an albumin binding domain and a mutant or wild type p53 peptide, as well as pharmaceutically acceptable salts of the compounds. In addition, methods for inducing an immune response in a subject and methods of administering such compounds to induce an immune response in a subject are disclosed herein.