The present invention provides recombinant adenoviral compositions and methods for their use in treating disorders associated with epithelial tissues.

The present invention relates to methods of treating a disease characterised by aberrant cell proliferation (e.g., a cancer) in a human subject in need thereof. In particular, the present invention relates to treating the above conditions by administering a therapeutically effective amount of at least one agent that increases activation of a receptor of at least one type II interferon and/or type I interferon, and administering to the subject at least one agent that inhibits the Hedgehog (Hh) signalling pathway (e.g., Vismodegib). Also provided are pharmaceutical compositions, including controlled release pharmaceutical compositions, containing at least one agent that increases activation of a receptor of at least one type II interferon and/or type I interferon (e.g., a checkpoint inhibitor), an inhibitor of Hh signalling pathway, and a controlled release matrix such as a SiO.sub.2 matrix gel.

The present invention relates to methods of treating a disease characterised by aberrant cell proliferation (e.g., a cancer) in a human subject in need thereof. In particular, the present invention relates to treating the above conditions by administering a therapeutically effective amount of at least one agent that increases activation of a receptor of at least one type II interferon and/or type I interferon, and administering to the subject at least one agent that inhibits the Hedgehog (Hh) signalling pathway (e.g., Vismodegib). Also provided are pharmaceutical compositions, including controlled release pharmaceutical compositions, containing at least one agent that increases activation of a receptor of at least one type II interferon and/or type I interferon (e.g., a checkpoint inhibitor), an inhibitor of Hh signalling pathway, and a controlled release matrix such as a SiO.sub.2 matrix gel.

The invention relates to a recombinant adeno-associated virus (AAV) capsid protein, which is a peptide-modified hybrid between AAV serotype 9 (AAV9) and AAV serotype 74 (AAVrh74) capsid proteins comprising at least one copy of a peptide comprising the RGD motif, wherein said recombinant peptide-modified hybrid AAV capsid protein has a further reduced liver tropism and an increased muscle transduction compared to the recombinant hybrid AAV capsid protein not having said peptide. The invention relates also to the derived peptide-modified hybrid AAV serotype vector particles packaging a gene of interest and their use in gene therapy, in particular for treating neuromuscular genetic diseases, in particular muscular genetic diseases.

The invention relates to a recombinant adeno-associated virus (AAV) capsid protein, which is a peptide-modified hybrid between AAV serotype 9 (AAV9) and AAV serotype 74 (AAVrh74) capsid proteins comprising at least one copy of a peptide comprising the RGD motif, wherein said recombinant peptide-modified hybrid AAV capsid protein has a further reduced liver tropism and an increased muscle transduction compared to the recombinant hybrid AAV capsid protein not having said peptide. The invention relates also to the derived peptide-modified hybrid AAV serotype vector particles packaging a gene of interest and their use in gene therapy, in particular for treating neuromuscular genetic diseases, in particular muscular genetic diseases.

Safe, rapid, and efficient methods for producing antigen-specific T cells recognizing human papilloma virus (HPV antigens); HPV-specific T cells, and methods for treating HPV infections and HPV-related malignancies by adoptive transfer of HPV-specific T cells.

Safe, rapid, and efficient methods for producing antigen-specific T cells recognizing human papilloma virus (HPV antigens); HPV-specific T cells, and methods for treating HPV infections and HPV-related malignancies by adoptive transfer of HPV-specific T cells.

There is provided inter alia an isolated polynucleotide, wherein the polynucleotide encodes a polypeptide selected from the group consisting of: (a) a polypeptide having the amino acid sequence according to SEQ ID NO: 1, (b) a functional derivative of a polypeptide having the amino acid sequence according to SEQ ID NO: 1, wherein the functional derivative has an amino acid sequence which is at least 80% identical over its entire length to the amino acid sequence of SEQ ID NO: 1, and (c) a polypeptide having the amino acid sequence according to SEQ ID NO: 3.

There is provided inter alia an isolated polynucleotide, wherein the polynucleotide encodes a polypeptide selected from the group consisting of: (a) a polypeptide having the amino acid sequence according to SEQ ID NO: 1, (b) a functional derivative of a polypeptide having the amino acid sequence according to SEQ ID NO: 1, wherein the functional derivative has an amino acid sequence which is at least 80% identical over its entire length to the amino acid sequence of SEQ ID NO: 1, and (c) a polypeptide having the amino acid sequence according to SEQ ID NO: 3.

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.