Oncolytic virus adjunct therapy with agents that increase virus infectivity
AssigneeGenelux Corporation
InventorsAladar A. Szalay, Joseph Cappello, Nanhai G. Chen, Boris Minev
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Abstract
Provided are adjunct therapies for use in combinations and compositions with an oncolytic virus, such as a vaccinia virus. The adjunct therapies include co-administration and co-formulation of a complement inhibitor and/or a lipid emulsion composition with the oncolytic virus. Also provided herein are therapeutic methods using the adjunct therapies for treatment of disease and conditions employing an oncolytic therapeutic virus, such as for the treatment of hyperproliferative diseases or conditions including tumors or cancers.
Claims25
A method of increasing infectivity of an oncolytic virus, comprising administering the oncolytic virus and an anti-C5 antibody to a subject, wherein:
- the oncolytic virus is a vaccinia virus;
- the virus and antibody are administered separately, in the same composition, sequentially or intermittently;
- the antibody binds to the alpha chain of complement C5, and is selected from among eculizumab, pexelizumab, TSA12/22 and MB12/122, and variants thereof that bind to the C5 alpha chain;
- the variants of eculizumab and pexelizumab specifically bind to the alpha chain of human complement component C5, and a) inhibit complement activation in a human body fluid, b) inhibit the binding of purified human complement component C5 to either human complement component C3 or human complement component C4, and c) do not specifically bind to the human complement activation product free C5a;
- the variants of TSA12/22 and MB12/122 specifically bind to C5 alpha chain of the C5 component of the complement system and recognize the region corresponding to residues 727-744 of SEQ ID NO:
- 53 of the C5 component of human complement or a region having at least 80% homology thereto, wherein the antibody inhibits the conversion of the C5 alpha chain to C5a and C5b, a light chain of the antibody is a lambda chain or a kappa chain, and a variable region of a heavy chain is the VH3 region;
- and
- the anti-C5 antibody is administered in an amount effective for inhibiting complement activation in a subject.
A composition, comprising, in a pharmaceutically acceptable carrier:
- an oncolytic virus, wherein the oncolytic virus is a vaccinia virus;
- and
- an anti-complement component 5 (C5) antibody that binds to the C5 alpha chain and is selected from among eculizumab, pexelizumab, TSA12/22 and MB12/122, and variants thereof that bind to the C5 alpha chain, wherein:
- the variants of eculizumab and pexelizumab specifically bind to the alpha chain of human complement component C5, and a) inhibit complement activation in a human body fluid, b) inhibit the binding of purified human complement component C5 to either human complement component C3 or human complement component C4, and c) do not specifically bind to the human complement activation product free C5a;
- the variants of TSA12/22 and MB12/122 specifically bind to C5 alpha chain of the C5 component of the complement system and recognize a region corresponding to residues 727-744 of SEQ ID NO:
- 53 of the C5 component of human complement or a region having at least 80% homology thereto, wherein the variant antibody inhibits the conversion of the C5alpha chain to C5a and C5b, a light chain of the antibody is a lambda chain or a kappa chain, and a variable region of a heavy chain is the VH3 region;
- and
- the anti-C5 antibody is in an amount effective for inhibiting complement activation in a subject.
A combination, comprising:
- a first composition comprising an oncolytic virus, wherein the oncolytic virus is a vaccinia virus;
- and
- a second composition comprising an anti-C5 antibody that binds to the C5 alpha chain, and is in an amount effective for inhibiting complement activation in a subject, wherein the anti-C5 antibody is selected from among eculizumab, pexelizumab, TSA12/22 and MB12/122, and variants thereof that bind to the C5 alpha chain, wherein:
- the variants of eculizumab and pexelizumab specifically bind to the alpha chain of human complement component C5, and a) inhibit complement activation in a human body fluid, b) inhibit the binding of purified human complement component C5 to either human complement component C3 or human complement component C4, and c) do not specifically bind to the human complement activation product free C5a;
- the variants of TSA12/22 and MB12/122 specifically bind to C5 alpha chain of the C5 component of the complement system and recognize the region corresponding to residues 727-744 of SEQ ID NO:
- 53 of the C5 component of human complement or a region having at least 80% homology thereto, wherein the antibody inhibits the conversion of the C5 alpha chain to C5a and C5b, wherein a light chain of the antibody is a lambda chain or a kappa chain, and a variable region of a heavy chain is the VH3 region.
Dependencies are inferred from the claim text.