Abstract: An adenovirus comprising a sequence of formula (I) 5?ITR-B1-BA-B2-BX-BB-BY-B3-3?ITR wherein BY 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.

Abstract: 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.

Abstract: An adenovirus comprising a sequence of formula (I) 5?ITR-B1-BA-B2-BX-BB-BY-B3-3?ITR wherein By comprises a transgene cassette containing four transgenes, said genes encoding a FAP-BITE, CXL10, CXL9, and IFN. The disclosure also extends to a pharmaceutical composition comprising the virus, and use of the virus or formulation in treatment.

Abstract: 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.

Abstract: A connector assembly and method of making and ensuring a reliable, fluid-tight connection, the assembly includes a housing a having a wall bounding a bore extending along a central longitudinal axis. The wall has a locking opening, a slot, and a window. A retaining member has a cylindrical wall received in the bore of the housing. The cylindrical wall has a detent received in the locking opening and a locking arm cantilevered by a hinge connection for pivotal movement. The locking arm is spaced from the cylindrical wall by a gap and is received in the slot when the detent is received in the locking opening. A visual indicator attached to the cylindrical wall moves radially outwardly into the window in response to the collar being fully received in the gap to provide visual evidence of a fluid-tight seal between the insertion member and the housing.

Abstract: A connector assembly and method of making and ensuring a reliable, fluid-tight connection is provided. The assembly includes a housing a having a wall bounding a bore extending along a central longitudinal axis. The wall has a locking opening, a slot, and a window. A retaining member has a cylindrical wall received in the bore of the housing. The cylindrical wall has a detent received in the locking opening and a locking arm cantilevered by a hinge connection for pivotal movement. The locking arm is spaced from the cylindrical wall by a gap and is received in the slot when the detent is received in the locking opening. A visual indicator attached to the cylindrical wall moves radially outwardly into the window in response to the collar being fully received in the gap to provide visual evidence of a fluid-tight seal between the insertion member and the housing.

Abstract: An RNAi agent targets a component of a human Notch signalling pathway other than presenilin1 or presenilin2 by RNA interference to reduce expression of said component.

Abstract: A product is disclosed comprising i) a modulator of the Notch signalling pathway; and ii) an autoantigen or bystander antigen, or a polynucleotide coding for an autoantigen or bystander antigen; as a combined preparation for simultaneous, contemporaneous, separate or sequential use for modulation of immune response.

Abstract: A method is provided for reducing an immune response to an allergen or antigenic determinant thereof in a mammal by administering a modulator of the Notch signalling pathway.

Abstract: Provided is a particle capable of being inserted into or taken up by a cell comprising i) a polynucleotide coding for a modulator of Notch signalling; and ii) a polynucleotide coding for an antigen or antigenic determinant thereof. Methods for using the particles are also described.

Abstract: There is provided a use of a modulator of Notch signalling for the preparation of a medicament for treatment of Graft Versus Host Disease (GVHD) and diseases and conditions caused by or associated with transplants such as organ, tissue and/or cell transplants (e.g. bone marrow transplants), wherein the modulator is used to reduce the reactivity of cells of the immune system.

Abstract: Provided is a method for modifying IL-4 expression in a cell using a modulator of Notch signalling. Also provided are methods for generating immune modulatory cytokine profiles with increased IL-4 expression and/or increased IL-10 expression and/or reduced IL-5, IL-13 and TNF? expression. In addition, a method for increasing a TH2 immune response and/or decreasing a TH1 immune response in a cell, using a modulator of Notch signalling, is provided. Methods of treatment are also disclosed.

Abstract: Provided is method for modulating the immune system in a mammal by simultaneously, contemporaneously, separately or sequentially administering to the mammal an effective amount of a modulator of the Notch signalling pathway; and an effective amount of an interferon or a polynucleotide encoding an interferon.

Abstract: A method for modulating the immune system in a mammal is described comprising simultaneously, contemporaneously, separately or sequentially administering: i) an effective amount of an agonist of Notch signalling; and ii) an effective amount of an immunosuppressive agent.

Abstract: Conjugates comprising a plurality of modulators of the Notch signalling pathway chemically bound to a support structure are described. The conjugates are useful for modulation of the Notch signalling pathway and treatment of associated conditions.

Abstract: Provided is a Notch ligand protein or polypeptide comprising a Notch ligand DSL domain; 1 to 5 (but no more than 5) Notch ligand EGF repeat domains; optionally, all or part of a Notch ligand N-terminal domain; and optionally, one or more heterologous amino acid sequences. Also provided is a homogeneous or heterogeneous multimer of the protein or polypeptide and a polynucleotide encoding the Notch ligand protein or polypeptide. An immune response can be modified in a subject by administering the Notch ligand protein or polypeptide to the subject.

Abstract: A method is disclosed for therapeutic modulation of Notch signalling by administering a construct comprising a multiplicity of bond, linked or immobilised modulators of Notch signalling.

Abstract: A method is described for modifying chemokine signalling by administering an effective amount of a modulator of the Notch signalling pathway. Human homologues of certain proteins, polypeptides and polynucleotides involved in Notch and/or chemokine signalling pathways are also described.

Abstract: An inhibitor of the Notch signalling pathway is provided for use as an immunostimulant, for example as a vaccine adjuvant.

Abstract: A method for detecting modulators of Notch signalling is described. The method includes the step of monitoring Notch signalling in a cell of the immune system in the presence of a candidate modulator.