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.

The invention discloses a human adenovirus species C having a capsid which comprises a modified adenovirus hexon protein, wherein the modified adenovirus hexon protein has a modified HVR1 region, wherein the modified HVR1 region has the sequence DEAATALEINLKKKKQAEQQ (SEQ ID NO.: 1). The invention further discloses the adenovirus of the disclosure for use in treating or preventing a human disease. The invention further discloses a nucleic acid encoding the modified adenovirus hexon protein. The invention further discloses the use of an adenovirus according to the disclosure for transducing mesenchymal stromal cells (MSCs) or tumor cells. The invention further discloses an in vitro method for transducing MSCs and a transduced MSC obtainable by the method. The invention further discloses the transduced MSC of the disclosure for use in treating a disease.

This invention relates to preparations comprising adenoviral vectors with modified capsid proteins. These modified capsid proteins enable customisable decoration of the adenoviral vector to be performed, enabling diverse applications from personalised cancer vaccines to targeted gene therapy vectors, and mixtures of the same. In particular, the adenoviral vectors with modified capsid proteins may be modified in the hexon and/or pIX capsid proteins. The invention makes use of peptide pairs to provide a “primed” adenovirus which is ready for decoration.

This invention relates to preparations comprising adenoviral vectors with modified capsid proteins. These modified capsid proteins enable customisable decoration of the adenoviral vector to be performed, enabling diverse applications from personalised cancer vaccines to targeted gene therapy vectors, and mixtures of the same. In particular, the adenoviral vectors with modified capsid proteins may be modified in the hexon and/or pIX capsid proteins. The invention makes use of peptide pairs to provide a “primed” adenovirus which is ready for decoration.

The present invention relates to methods and materials useful for systemically delivering polynucleotides across the blood brain barrier using adeno-associated virus as a vector. For example, the present invention relates to methods and materials useful for systemically delivering α-N-acetylglucosamidinase polynucleotides to the central and peripheral nervous systems, as well as the somatic system. Use of these methods and materials is indicated, for example, for treatment of the lysosomal storage disorder mucopolysaccharidosis IIIB. As another example, the present invention relates to methods and materials useful for systemically delivering N-sulphoglucosamine sulfphohydrolase polynucleotides to the central and peripheral nervous systems, as well as the somatic system. Use of this second type of methods and materials is indicated, for example, for treatment of the lysosomal storage disorder mucopolysaccharidosis IIIA.

The present invention relates to methods and materials useful for systemically delivering polynucleotides across the blood brain barrier using adeno-associated virus as a vector. For example, the present invention relates to methods and materials useful for systemically delivering α-N-acetylglucosamidinase polynucleotides to the central and peripheral nervous systems, as well as the somatic system. Use of these methods and materials is indicated, for example, for treatment of the lysosomal storage disorder mucopolysaccharidosis IIIB. As another example, the present invention relates to methods and materials useful for systemically delivering N-sulphoglucosamine sulfphohydrolase polynucleotides to the central and peripheral nervous systems, as well as the somatic system. Use of this second type of methods and materials is indicated, for example, for treatment of the lysosomal storage disorder mucopolysaccharidosis IIIA.

This present disclosure provides adeno-associated viral vectors, recombinant adeno-associated vims (rAAV), and methods of their use in gene therapy for treating CDKL5 deficiency disorder (CDD). Also provided are pharmaceutical compositions comprising an rAAV of the invention and a pharmaceutically acceptable carrier or excipient. These pharmaceutical compositions may be useful in gene therapy for the treatment of CDD caused by mutations in CDKL.

This present disclosure provides adeno-associated viral vectors, recombinant adeno-associated vims (rAAV), and methods of their use in gene therapy for treating CDKL5 deficiency disorder (CDD). Also provided are pharmaceutical compositions comprising an rAAV of the invention and a pharmaceutically acceptable carrier or excipient. These pharmaceutical compositions may be useful in gene therapy for the treatment of CDD caused by mutations in CDKL.

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.