31results 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.

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.

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.

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.

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 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.

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.

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.

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.

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.

Provided are a signaling ribonucleic acid (mRNA) comprising a 5'non-translated region (5 'UTR), a sequence encoding a p53 protein, and a 3' non-translated region (3 'UTR), a composition comprising the signaling ribonucleic acid for delivering the signaling ribonucleic acid or p53 to a subject, and a composition and method for preventing or treating cancer.

The invention is based on designed ankyrin repeat proteins (DARPins) specifically binding to a DNA binding domain of human p53. The DARPins of the invention are capable of forming a binding interface with the DNA binding domain of p53, and upon binding facilitate p53 protein stability. The DARPins of the invention are for use in the treatment of p53 related diseases such as cancer. Further, the invention pertains to nucleic acid constructs encoding the DARPin of the invention, methods for their production and cells comprising the DARPins or nucleic acid constructs of the invention.

The invention relates to new methods and approaches for the treatment of cancers, particularly cancers expressing TP53 mutations, comprising the administration of a Sting agonist, and either an anti-cancer immunotherapy, or a TP53 targeting cancer therapy.

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.

The invention relates to short peptides, of amino acids in length, capable of binding with high affinity to the MDM2 protein and interfering with the MDM2 / MDM4 heterodimer activity, thereby hindering the inhibitory function of the heterodimer against the tumor suppressor p53. The invention also relates to the use of the aforementioned peptides, or nucleic acid molecules encoding them, in the treatment of a tumor, preferably a solid tumor expressing wild-type p53.

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

Disclosed are p53 peptidomimetic macrocycles, each p53 peptidomimetic macrocycle comprising an i, i + 4 olefin staple and a polypeptide tail covalently linked to the p53 peptidomimetic macrocycle; an i, i + 7 olefin staple and a polypeptide tail covalently linked to the p53 peptidomimetic macrocycle; or, an i, i + 7 di-alkyne staple and optionally a polypeptide tail covalently linked to the p53 peptidomimetic macrocycle; wherein the p53 peptidomimetic macrocycle comprises all D-configuration amino acids and the polypeptide tail comprises three to nine amino acids, each amino acid of the polypeptide tail independently having a D-configuration or an L-configuration. The p53 peptidomimetic macrocycles are protease resistant, cell permeable without inducing membrane disruption, and intracellularly activate p53 by binding MDM2 and MDMX, thereby antagonizing MDM2 and MDMX binding to p53. These p53 peptidomimetic macrocycles may be useful in anticancer therapies, particularly in combination with chemotherapy or radiation therapy.

Disclosed are p53 peptidomimetic macrocycles, wherein each p53 peptidomimetic macrocycle comprises an i,i+4 olefin staple and a polypeptide tail covalently attached to the p53 peptidomimetic macrocycle; an i,i+7 olefin staple and a polypeptide tail covalently attached to the p53 peptidomimetic macrocycle; or an i,i+7 dialkyne staple and an optional polypeptide tail covalently attached to the p53 peptidomimetic macrocycle, wherein the p53 peptidomimetic macrocycle comprises amino acids that are all in the D-configuration, the polypeptide tail comprises 3-9 amino acids, and each amino acid in the polypeptide tail independently has the D- or L-configuration. The p53 peptidomimetic macrocycles are protease resistant and cell permeable without inducing membrane disruption, and activate p53 in cells by binding to MDM2 and MDMX, thereby antagonizing the binding of MDM2 and MDMX to p53. These p53 peptidomimetic macrocycles may be useful in anti-cancer therapy, especially in combination with chemotherapy or radiation therapy.

Compositions and methods are provided for potent mRNA vaccines for treatment of cancer with mutations in ras gene family multiplexed with TP53. The compositions include a pharmaceutical composition containing mRNA molecules encoding multiple peptides of a group of somatic mutations together with a pharmaceutically acceptable carrier. Methods for stimulating system immune responses and treatment are provided, including intratumoral, intravenous, intramuscular, intradermal, and subcutaneous injection.