An oncolytic virus (for example a replication competent virus) comprising a transgene cassette encoding an anti-CD40 antibody or binding fragment thereof, wherein the transgene cassette comprises an amino acid sequence given in SEQ ID NO: 12 or a sequence at least 95% identical thereto (such as 96, 97, 98 or 99% identical thereto), in particular a cassette of SEQ ID NO: 12; pharmaceutical compositions comprising the same, methods of preparing said oncolytic virus and compositions and use of the oncolytic virus or composition in treatment, in particular in the treatment of cancer. Also provided is the treatment of a patient population characterised as having a cancer expressing CD40, in particular a cancer over expressing CD40, with a therapy according to the present disclosure.

Methods of treating a subject having a brain tumor comprising (a) administering an oncolytic virus and (b) administering a therapeutic antibody to said subject.

The invention concerns APCs, such as DCs, comprising a combination of an exogenous type I interferon and an exogenous CD40-L or one or more heterologous nucleic acid sequences encoding a combination of an exogenous type I IFN and an exogenous CD40-L, such as a combination of IFNβ and CD40-L; and methods for treating a malignancy by administering such APCs to a subject in need thereof. In certain embodiments, a subject is treated with an irradiation therapy before administering the APCs, such as DCs, of the invention. The invention also concerns an oncolytic virus comprising a combination of a type I IFN and CD40-L or one or more nucleic acid sequences encoding a combination of a type I IFN and CD40-L, such as a combination of IFNβ and CD40-L; and methods for treating a malignancy by administering such oncolytic virus to a subject in need thereof.

The invention disclosed herein describes biomarkers useful for prognosis, selection and monitoring of oncolytic virus therapy for patients with various types of cancer. In particular, the present invention provides identification of proteins whose expression patterns are strongly predictive of the outcome of oncolytic virus therapy in a patient with cancer. The present invention provides a method for identifying and selecting cancer patients who are likely to be non-responsive to onocolytic virus therapy. These patients can be co-administered an agent that stimulates a cell-mediated immune response in the patient with the oncolytic virus or can be administered a therapy other than oncolytic virus therapy.

The present disclosure involves compositions and methods for treating brain cancers having mutations in the retinoblastoma (Rb) pathway using an oncolytic adenovirus comprising an alteration in the Rb binding site of E1A, and a targeting motif inserted in the Ad fiber protein. The adenovirus is able to kill the tumor cells without harming cells with a wild-type retinoblastoma pathway.

An adenovirus comprising a sequence of formula (I) 5′ITR-B.sub.1-B.sub.A-B.sub.2-B.sub.X-B.sub.B-B.sub.Y-B.sub.3-3′ITR wherein B.sub.Y comprises a transgene cassette containing four transgenes, said genes encoding a FAP-Bispecific T cell activator, CXL10, CXL9, and IFN. The disclosure also extends to a pharmaceutical composition comprising the virus, and use of the virus or formulation in treatment.

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 disclosure relates to a group B adenovirus comprising a sequence of formula (I): 5′ITR-B1-BA-B2-BX-BB-BY-B3-3′ITR wherein: B1 is bond or comprises: E1A, E1B or E1A-E1B; BA comprises-E2B-L1-L2-L3-E2A-L4; B2 is a bond or comprises: E3; BX is a bond or a DNA sequence comprising: a restriction site, one or more transgenes or both; BB comprises L5; BY is a bond or a DNA sequence comprising: a restriction site, one or more transgenes or both; B3 is a bond or comprises: E4; wherein at least one of BX or BY is not a bond, pharmaceutical compositions comprising the same and use of the viruses and compositions in treatment, particularly in the treatment of cancer. The disclosure also extends to plasmids and processes employed to prepare the said viruses.

The present invention provides an agent for protecting the liver and/or promoting liver regeneration, which contains a heparin-binding EGF-like growth factor-like growth factor (HB-EGF) or a partial peptide thereof, or a nucleic acid that encodes same, and an agent for the prophylaxis or treatment of liver diseases. The present invention further provides a method for producing a cell for liver protection and/or promoting liver regeneration, and for the prophylaxis/treatment of a liver disease, which includes introducing a nucleic acid that encodes HB-EGF or a partial peptide thereof into a cell collected from an animal.

The invention provides an in vivo individualized systemic immunotherapeutic method and device. The method includes, in a non-sequential manner: (1) increasing release amount of tumor antigens at a tumor site; (2) at the tumor site, increasing level of proteins capable of adhering to and/or wrapping the tumor antigens; (3) at the tumor site, increasing level of dedicated antigen-presenting cells involved in immunity, and establishing, between the dedicated antigen-presenting cells and immune effector cells, a close connection capable of activating the immune effector cells; and (4) at the tumor site, increasing level and improving function of the immune effector cells. The steps (1)-(4) each reaches a maximum value at a respective time which overlaps with each other maximally, as well as at a respective site which overlaps with each other maximally. The invention combines oncolytic therapy and immunotherapy, in individualized systemic immunotherapy, and provides significantly improved therapeutic effect.