The present invention provides methods for treating an individual having solid or lymphatic tumor comprising locally administering to the site of the tumor an oncolytic virus, and systemically administering an immunomodulator (including a combination of immunomodulators). The methods may further comprise local administration to the site of the tumor a second immunomodulator (including a combination of immunomodulators). Also provided are compositions and kits for the cancer therapy methods.

Recombinant adenoviral vectors, immunogenic compositions thereof and their use in medicine, and methods for generating recombinant adenoviral vectors are provided. In particular, the an adenovirus vector having a capsid derived from chimpanzee adenovirus AdY25, wherein the capsid encapsidates a nucleic acid molecule comprising an exogeneous nucleotide sequence of interest are provided.

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.

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 provides methods for treating an individual having solid or lymphatic tumor comprising locally administering to the site of the tumor an oncolytic virus, and systemically administering an immunomodulator (including a combination of immunomodulators). The methods may further comprise local administration to the site of the tumor a second immunomodulator (including a combination of immunomodulators). Also provided are compositions and kits for the cancer therapy methods.

Modified E1a regulatory sequences are provided, wherein at least one Pea3 binding site, or a functional portion thereof, is deleted. Also provided are modified E1a sequences that selectively express particular isoforms. Also provided is an E1b-19K clone insertion site. These modified sequences can be used individually, or in combination with one another, to provide tumor-selective expression of proteins.

The present invention relates to the use of gasdermin, in particular of gasdermin A, gasdermin B, gasdermin C, gasdermin D, DFNA5 or DFNB59 (or pejvakin), and more particularly pejvakin for modulating cellular redox homeostasis. A particularly preferred use of gasdermin, in particular of gasdermin A, gasdermin B, gasdermin C, gasdermin D, DFNA5 or DFNB59 (or pejvakin), and more particularly pejvakin in the context of the present invention is as an antioxidant. The present invention also concerns a virally-mediated gene therapy for restoring genetically-impaired auditory and vestibular functions in subjects suffering from an Usher syndrome. More precisely, this gene therapy takes advantage of an AAV2/8 vector expressing at least one USH1 gene product, preferably SANS.

Provided are an LncRNA and oncolytic adenovirus, and application thereof. The oncolytic adenovirus is used as a carrier to express the LncRNA, so as to express the LncRNA in a cancer cell; competitively binding a target gene of OncomiRs, and consuming the OncomiRs, thus protecting a cancer suppressor gene from interference and suppression of the OncomiRs, and achieving target intervention therapy of the cancer cell.

A Process for the Production of Adenovirus The present disclosure relates to a continuous process for the manufacture of an adenovirus wherein the process comprises the steps: A) continuously culturing, in a vessel, mammalian cells infected with the adenovirus in the presence of media suitable for supporting the cells such that the virus replicates, wherein the cells are capable of supporting viral replication, and B) isolating from the media the virus produced from step a) wherein the isolation of virus is not subsequent to a cell lysis step, wherein viable cells for virus infection and production are maintained in the vessel at a level suitable for replicating the virus for the period of continuous manufacture, wherein the process comprises at least one media change or addition and at least one cell change or addition. The disclosure also extends to viruses populations obtained or obtainable from the method.

The present disclosure provides a method of treating a human patient comprising the steps of: systemically administering multiple doses of a parenteral formulation of a replication capable oncolytic adenovirus of subgroup B in a single treatment cycle, wherein the total dose given in each dose is in the range of 1×10.sup.10 to 1×10.sup.14 viral particles, and wherein each dose of virus is administered over a period of 1 to 90 minutes, for example at a rate of viral particle delivery in the range of 2×10.sup.10 particles per minute to 2×10.sup.12 particles per minute. The disclosure further extends to formulations of the said oncolytic adenoviruses and combination therapies of the viruses and formulations with other therapeutic agents.