The invention relates to a recombinant adenovirus comprising an albumin-binding moiety on the outer surface of the adenoviral hexon protein, pharmaceutical compositions containing it and its medical use. Particularly, the invention relates to an oncolytic adenovirus comprising a sequence encoding an albumin-binding moiety inserted in the hypervariable region 1 (HVR1) of the hexon protein coding sequence and its use in the prevention and/or treatment of cancer.

This invention relates to the use of an adenovirus to treat cancer, for example. The adenovirus may be replication deficient in cells that lack Y box binding protein. The adenovirus may encode an oncogene or an oncogene product, which may transactivate at least one viral gene.

The present disclosure describes the generation and the use of Ad variants (Ad) possessing any combination of mutations in genes that code for the hexon, penton, fiber, and non-structural proteins, where simultaneous modification of hexon and penton are made to avoid the trapping of Ad in the liver and to reduce toxicity after intravascular virus administration. Such liver de-targeted Ad can be useful tool for selective and specific gene delivery to extra-hepatic tissues and cells, including disseminated metastatic cancer cells.

The present disclosure provides SETD7 modulators (e.g., polypeptides, polynucleotides, vectors, compositions, micelles, or pharmaceutical composition) which reduce or abolish SETD7 translocation to the nucleus, e.g., in response to stimuli such as increases in glucose levels. In some aspects, the SETD7 modulators mimic phosphorylated STED7, competing with STED7 and reducing or abolishing SETD7 nuclear translocation. In turn, the reduced SETD7 nuclear translocation results in a decrease in histone monomethylation. In some aspects, the SETD7 modulator is a catalytically inactive SETD7 protein. In some aspects, the SETD7 modulator is a polypeptide (e.g., a phosphomimetic polypeptide). In other aspects, the SETD7 modulator is a polynucleotide encoding a SETD7 polypeptide modulator, e.g., a phosphomimetic polypeptide or a mutant SETD7 protein. The SETD7 modulators of the present disclosure can be used to treat type diabetes or cancer.

Oncolytic adenoviruses capable of selectively replicating in tumor cells deficient in p53 transcriptional activity are described. Recombinant adenovirus genomes that encode the p53-selective adenoviruses are also described. The recombinant adenoviruses and adenovirus genomes, or compositions thereof, can be used, for example, to reduce or inhibit tumor progression, or reduce tumor volume in a subject with a tumor having dysregulated p53 activity.

Recombinant adenovirus genomes that include a synthetic transcriptional circuit are described. Synthetic adenoviruses positively regulated using two-step transcriptional amplification (TSTA) are further described. Selection of the heterologous promoter is based on the desired replication characteristics of the synthetic virus. For example, the heterologous promoter can be a constitutive promoter, a tumor-specific promoter or a tissue-specific promoter.

The present invention relates to the preparation of mesenchymal stem cells, which are for the proliferation of viral vectors and viruses, and enable virus production and release timing control such that tumor targeting can be improved and viruses can be mass-produced. In addition, the tumorigenesis of mesenchymal stem cells of the present invention can be fundamentally blocked, safety is secured by enabling virus production and release to be controlled at desired time points, and antitumor effects can be maximized.

Provided herein is a conditionally-replicating serotype 5 adenovirus or adenoviral vector expressing a mutant E1A protein under control of a promoter that is responsive to hypoxia and inflammation and one or more immune modulators under control of a tumor-specific promoter. The adenovirus or adenoviral vector also comprises serotype 3 fiber and hexon proteins. Also provided is a method of inducing cytotoxicity in tumor cells using a composition containing the adenovirus or adenoviral vector.

The present disclosure concerns combination therapy for cancer thatutilizes (i) an oncolytic virus; (ii) a virus comprising nucleic acid encoding an immunomodulatory factor; and (iii) at least one cell comprising a chimeric antigen receptor (CAR) specific for a cancer cell antigen. In particular embodiments, the virus comprises nucleic acid encoding an immunomodulatory factor comprises nucleic acid encoding IL-12 and/or antagonist anti-PD-L1 antibody.

The present invention relates to a technique for effective intranasal delivery to the brain. More specifically, the present invention is used for diagnosing, preventing or treating central nervous system encephalopathy, neurodegenerative diseases or brain tumor by effectively delivering to the brain a pH-responsive and bioreducible PPA polymer, which can be used as a drug carrier, by means of nasal administration.