64results 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.

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 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.

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.

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.

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.

The invention relates to genetically engineered mouse models for multiple myeloma (MM) and their uses thereof for the development of multiple myeloma models as well as for the screening of compounds suitable for the treatment of multiple myeloma.

23. The use of one or more senescence inhibitors to increase survival and / or engraftment of hematopoietic cells, hematopoietic stem cells, hematopoietic progenitor cells and / or T cells in gene therapy.

The invention provides a plasmid tool for simulating Kras random evolution and application thereof, and the plasmid tool comprises at least two guide RNA expression cassettes driven by a first promoter, which respectively target a Pten gene and a Trp53 gene; the pilot editing guide RNA expression box is driven by a second promoter, targets the 12th codon of the Kras gene, and comprises a repair template sequence for editing the codon into G12D; the fusion protein expression cassette is driven by a third promoter and comprises SpCas9 protein and MMLV reverse transcriptase; and at least one eukaryotic selection marker gene expression cassette. The invention also discloses a method for constructing a simulated Kras random evolution model by adopting the plasmid tool, and application of the plasmid tool in screening targeted drugs aiming at KRAS mutation tumors. The plasmid tool provided by the invention can realize cell multi-gene locus editing, construct a Kras locus random evolution model and simulate a Kras random evolution process in ovarian cancer.

Disclosed are isolated or purified T cell receptors (TCRs) having antigenic specificity for human p53Y220C or human p53R175H. 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 suppressors contribute to the development and progression of cancer. Disclosed herein are compounds and methods to recover wild-type function of p53 mutants using x-ray co-crystal structures of mutant p53 and compounds of the disclosure. The compounds of the present invention can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.

The invention belongs to the technical field of gene editing, and particularly relates to a construction method of a transgenic mouse with a tissue-specific precancerous marker. A fertilized ovum is constructed through a gene editing technology, a mutant p53 protein and a fluorescent protein are fused, a loxp-Stop-loxp sequence is added in front of a promoter of a mutant p53 sequence, the fertilized ovum is transplanted into a female mouse, the obtained progeny is an LPL transgenic mouse, and expression inhibition of the mutant p53 protein and the fluorescent protein is achieved; the LPL transgenic mouse is mated with a Cre tool mouse to obtain a transgenic mouse of which the offspring is a tissue-specific precancerous marker, the transgenic mouse expresses mutant p53 protein and fluorescent protein at a specific tissue, early tumor focus development is monitored and traced through a living body fluorescence imaging system, and the LPL transgenic mouse has extremely high application and research values.

To provide further treatment methods of cancer.SOLUTION: Also provided are: an isolated or purified T cell receptor (TCR) having antigenic specificity for human p53 having the G245S mutation; and related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.SELECTED DRAWING: Figure 1

An agent which promotes homology directed DNA repair for use in haematopoietic stem and / or progenitor cell gene therapy, wherein said haematopoietic stem cells are gene edited. Use of an agent which promotes homology directed DNA repair, for increasing the survival and / or engraftment of gene edited haematopoietic stemand / or progenitorcells or for increasing the efficiency of gene editing of haematopoietic stem and / or progenitor cells.

Provided herein are methods and compositions for treating cancer in an individual, comprising administering to the individual effective amounts of at least one CD122 / CD132 agonist, at least one immune checkpoint inhibitor, and a viral composition comprising one or more viruses modified 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 effective amounts of at least one oncolytic viral composition, at least one CD122 / CD132 agonist, and at least one immune checkpoint inhibitor. Also provided herein are methods for improving anti-tumor efficacy by administering the above-mentioned agents in combination with other cancer therapies. These treatments unexpectedly resulted in complete tumor remission and curative outcomes in highly aggressive forms of cancer that are generally known to be resistant to immunotherapy.