Compositions and methods for immune-mediated cancer therapy
AssigneeTeclison Limited
InventorRuey-min Lee
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Abstract
Disclosed herein are methods and compositions for enhancing an immune response to a solid tumor in a subject. In some embodiments, a method comprises: (a) administering to the subject a hypoxia-activated bioreductive agent (HABA); (b) inducing hypoxia by (i) administering a hypoxia-inducing agent to the subject or (ii) embolizing one or more blood vessels supplying the solid tumor; and (c) administering an immune checkpoint inhibitor prior to, simultaneously with, or subsequent to step (b) in an amount effective to enhance an immune response to the solid tumor, as compared to an immune response in the absence of the immune checkpoint inhibitor. Kits for use in the disclosed methods are also provided.
Claims10
A method of enhancing an anti-tumor immune response in a subject in need thereof, the method comprising:
- (a) administering a hypoxia-activated bioreductive agent (HABA) that is tirapazamine to said subject suffering from a cancer that has a liver tumor and a lung tumor, or a cancer that has microsatellite-stable metastatic colorectal cancer (mCRC-MSS) and a lung tumor;
- (b) inducing hypoxia by trans-arterial embolization of one or more blood vessels supplying said liver tumor or said mCRC-MSS, and
- (c) administering to said subject an effective amount of an immune checkpoint inhibitor of programmed cell death protein 1 (PD-1) to enhance an anti-tumor immune response in said subject, wherein said immune checkpoint inhibitor is an anti-PD-1 antibody, wherein the anti-PD-1 antibody is nivolumab or pembrolizumab;
- wherein the combination of (a) administering said HABA and (b) inducing hypoxia induces necrosis of said liver tumor or said mCRC-MSS;
- and
- wherein the combination of (a) administering the HABA, (b) inducing hypoxia, and (c) administering the anti-PD-1 antibody exhibits a synergistic effect, which wherein said synergistic effect comprises a size reduction of said lung tumor greater than a corresponding size reduction achieved in the absence of the combination of (a) administering said HABA and (b) inducing hypoxia, thereby enhancing said anti-tumor immune response in said subject.
Dependencies are inferred from the claim text.