Beta-catenin inhibitor combination therapy for cold tumors
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Solution Overview
Problem
Current cancer treatments using immunotherapy are ineffective for 'cold' or non-T cell inflamed tumors, which lack infiltrating CD8+ T cells and do not respond to checkpoint inhibitors.
Innovation Solution
Combining a β-catenin inhibitor, such as a nucleic acid inhibitor molecule, with immunotherapy to reduce β-catenin expression, converting non-inflamed tumors into inflamed tumors and enhancing the responsiveness to immunotherapy, even in tumors without an activated Wnt/β-catenin pathway.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunotherapy is used to treat cancer, then T cell activation is promoted and anti-tumor immune responses are enhanced, but the treatment is ineffective for cold or non-inflamed tumors that lack infiltrating T cells
Solution Approach 1:
The patent changes the immunological state parameter of the tumor microenvironment by reducing beta-catenin expression, which triggers a cascade of molecular changes including increased chemokine production and T cell recruitment signals, effectively converting the tumor from a cold to hot phenotype and enabling immunotherapy response
Solution Approach 2:
The patent introduces beta-catenin inhibition as an intermediary mechanism that mediates between the tumor microenvironment and immunotherapy effectiveness, where beta-catenin inhibitors serve as the connecting element that transforms the tumor state to make it responsive to checkpoint blockade therapy
2Reliability
If beta-catenin expression is reduced to convert cold tumors into hot tumors, then immunotherapy responsiveness is improved, but additional treatment complexity is introduced
Solution Approach 1:
The patent merges two therapeutic approaches into a single combination regimen: beta-catenin inhibition (via small molecules, peptides, antibodies, or nucleic acid inhibitors) combined with immunotherapy (checkpoint blockade), creating an integrated treatment that addresses both tumor intrinsic factors and immune system activation simultaneously
Data Source
AI summary
Provided herein are methods and compositions for treating cancer, including cancer that is not responsive to immunotherapy. In one aspect, the methods of treatment comprise administering to the subject a therapeutically effective amount of a β-catenin inhibitor and a therapeutically effective amount of an immunotherapeutic agent. Another aspect is directed to pharmaceutical compositions comprising a β-catenin inhibitor for use in treating cancer, wherein the composition is administered in combination with an immunotherapeutic agent. Yet another aspect is directed to a method of potentiating the therapeutic effect of immunotherapy against a cancer using a β-catenin inhibitor, such as a β-catenin nucleic acid inhibitor molecule.