Compositions and methods for immune-mediated cancer therapy
Inventors
Assignees
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Publication Number
US-12350275-B2
Publication Date
2025-07-08
Expiration Date
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.
Core Innovation
The described invention provides a method of treating a cancer in a subject having a solid liver tumor. The method includes administering tirapazamine to the subject, inducing trans-arterial embolization of one or more blood vessels supplying the liver of the subject, and administering nivolumab or pembrolizumab prior to, simultaneously with, or subsequent to inducing trans-arterial embolization.
The disclosed approach is directed to enhancing immune responses in the setting of solid tumors by combining a hypoxia-activated bioreductive agent with an intervention that induces tumor hypoxia. The disclosure links induction of hypoxia and tumor necrosis with antigen exposure and inflammatory infiltration, and then administering immune checkpoint inhibition using PD-1/PD-L1/CTLA-4 inhibitors, including nivolumab and pembrolizumab.
The disclosure further characterizes the embolization-related vasculature as blood vessels supplying the liver and optionally also supplying the solid liver tumor, including trans-arterial embolization approaches such as vascular occlusion/embolization and representative embodiments involving hepatic artery ligation and trans-arterial embolization.
Claims Coverage
The independent claims cover three variants of a solid liver tumor cancer treatment regimen using tirapazamine, trans-arterial embolization, and nivolumab or pembrolizumab with different timing relationships relative to inducing trans-arterial embolization. Across the independent claims, three main inventive features are recited: tirapazamine administration, inducing trans-arterial embolization of liver-supplying blood vessels, and immune checkpoint inhibitor administration (nivolumab or pembrolizumab) at specified time points relative to embolization.
Tirapazamine administration for solid liver tumor cancer treatment
Administering tirapazamine to the subject.
Inducing trans-arterial embolization of one or more blood vessels supplying the liver
Inducing trans-arterial embolization of one or more blood vessels supplying the liver of the subject.
Administering nivolumab or pembrolizumab with timing relative to trans-arterial embolization
Administering nivolumab or pembrolizumab to the subject prior to, simultaneously with, or subsequent to inducing trans-arterial embolization; in other variants, administering subsequent to inducing trans-arterial embolization, or prior to and subsequent to inducing trans-arterial embolization.
Across the independent claims, the inventive concept is the combined administration of tirapazamine and immune checkpoint inhibition (nivolumab or pembrolizumab) with trans-arterial embolization of one or more blood vessels supplying the liver of the subject, with the timing of immune checkpoint inhibitor administration differing among the claim variants.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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