Immunomodulatory oncolytic adenoviral vectors, and methods of production and use thereof for treatment of cancer
AssigneeTrieza Therapeutics, Inc.
InventorsDaniel Hicklin, Kenneth Nelson Wills, Cynthia Seidel-Dugan, William Winston, Philipp Steiner
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Abstract
Disclosed herein are compositions and methods for treating cancer in a subject. This involves administering an oncolytic virus containing a heterologous DNA sequence encoding one or more immunomodulatory and/or immunostimulatory polypeptide(s) of interest to the subject under conditions effective to enhance an anti-tumor immune response in the subject, and to treat cancer. It also relates to a method of enhancing the delivery to and distribution within a tumor mass of therapeutic viruses.
Claims5
A pharmaceutical composition comprising an effective amount of a recombinant adenoviral vector comprising:
- (a) a first transgene insertion site located between the start site of adenoviral E1b-19K and the start site of adenoviral E1b-55K;
- (b) a second transgene insertion site located in adenoviral E3 region;
- (c) a first DNA sequence encoding a first polypeptide selected from the group consisting of:
- a chimeric human IL-12, a human IL-7, an anti-CTLA-4 antibody, an IL-10Rtrap, a human CD70, a human IL-2 polypeptide, a human CD40 ligand, and a human OX40 ligand, wherein the first DNA sequence is present in the first transgene insertion site and is operably linked to a first endogenous promoter;
- (d) a second DNA sequence encoding a second polypeptide selected from the group consisting of:
- a chimeric human IL-12, a human IL-7, an anti-CTLA-4 antibody, an IL-10Rtrap, a human CD70, a human IL-2 polypeptide, a human CD40 ligand, and a human OX40 ligand, wherein the second DNA sequence is present in the second transgene insertion site and is operably linked to a second endogenous promoter;
- and
- (e) a modified adenoviral E1a regulatory sequence, wherein at least one Pea3 binding site of the adenoviral E1a regulatory sequence is modified or deleted.
Dependencies are inferred from the claim text.