Survival-targeting chimeric (SURTAC) molecules are provided herein, as well as methods for their use in removing ubiquitin molecules from ubiquitinylated proteins. In one embodiment, the SURTAC molecule comprises a first binding domain, a second binding domain, and a linker domain, wherein the first binding domain is configured to bind to an ubiquitinylated protein; the second binding domain is configured to bind to an ubiquitin protease that cleaves one or more ubiquitin from the ubiquitinylated protein bound to the first binding domain, and the linker domain is configured to link the first binding domain to the second binding domain.

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.

A protein-based peptide drug carrier derived from the tetramerization domain of the chimeric oncogenic protein Bcr/Abl of chronic myeloid leukemia. Peptides to be delivered are grafted to the N-terminal helical region of Bcr/Abl tetramer. To facilitate cellular uptake, an Arg-repeating hexapeptide is added to the C-terminal end of the Bcr/Abl protein. The protein-based delivery strategy provides a clinically viable solution to p53-inspired anticancer therapy and is applicable to the development of many other peptide therapeutics to target other intracellular protein-protein interactions responsible for disease initiation and progression.

Provided herein is a method of treating medulloblastoma or glioblastoma in a subject by administering to the subject a PI3K activator (e.g., thymosin β-4 or a derivative thereof) and one or more chemotherapeutic agents and/or radiation. The combination therapy is effective in the treatment of medulloblastoma or glioblastoma characterized by cells with elevated p53 levels.

Compositions, systems and methods of improving the health of the microbiome of an individual's skin relate to the provision of skin contacting formulations containing beneficial bacteria and other microbe components to foster the growth and maintenance of a healthy skin microbiome. Certain embodiments include methods of treatment for acne and other skin disorders involving the use of probiotics, as well as the use of bacteria engineered via CRISPR systems for the treatment of specific skin disorders.

An isolated peptide is provided. The peptide comprises an amino acid sequence arranged in a space and configuration that allow interaction of the peptide with the DNA Binding Domain (DBD) of p53 through at least one residue of the DBD by which pCAP 250 (SEQ ID NO: 1) binds the DBD, wherein the peptide at least partially reactivates a mutant p53 protein, with the proviso that the peptide is not SEQ ID NO: 59-382.

Provided herein are peptidomimetic macrocycles containing amino acid sequences with at least two modified amino acids that form an intramolecular cross-link that can help to stabilize a secondary structure of the amino acid sequence. Suitable sequences for stabilization include those with homology to the p53 protein. These sequences can bind to the MDM2 and/or MDMX proteins. Also provided herein are methods of using such macrocycles for the treatment of diseases and disorders, such as cancers or other disorders characterized by a low level or low activity of a p53 protein or high level of activity of a MDM2 and/or MDMX protein.

Disclosed are isolated or purified T cell receptors (TCRs) having antigenic specificity for human p53.sup.R273C or human p53.sup.Y220C. 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.

Described herein are immune cells comprising: a T-cell receptor (TCR) and a chimeric stimulating receptor (CSR) that comprises (i) a ligand-binding module that is capable of binding or interacting with a target ligand; (ii) a transmembrane domain; and (iii) a CD30 costimulatory domain, in which the CSR in the immune cells lacks a functional primary signaling domain. Also provided herein are methods of using the same or components thereof (e.g., the CSR) for therapeutic treatment of cancers (e.g., solid tumor cancers).

Treatment of cancer harboring mutations in the TP53 gene and/or post-translational modifications in the p53 protein. The present invention relates to the use of viruses belonging to the family Parvoviridae, genus Protoparvovirus, or combinations of such viruses with chemotherapy drugs, in the treatment of cancer. In particular the cancer is characterized by showing mutations in the TP53 gene and/or post-translational modifications in the p53 protein.