CD11b Agonists Repolarize Macrophages to Enhance Anti-Tumor Immunity
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Solution Overview
Problem
Current cancer treatments fail to effectively target the immunosuppressive functions of tumor-associated macrophages, which promote tumor progression and immune evasion, due to incomplete understanding of the molecular mechanisms regulating these functions.
Innovation Solution
Administering agonists of CD11b expression, such as miRNA Let7a or leukadherin 1 (LA1), in combination with chemotherapeutic agents like gemcitabine, pembrolizumab, or nivolumab, to modulate macrophage polarization and enhance anti-tumor immune responses by inhibiting immune suppression and promoting neovascularization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If agonists of CD11b expression are administered to modulate macrophage polarization, then anti-tumor immune responses are enhanced, but the complexity of the treatment regimen increases
Solution Approach 1:
The patent combines agonists of CD11b expression (such as anti-miRNA Let7a or leukadherin 1) with chemotherapeutic agents and/or immunotherapeutic agents into a single treatment regimen. This merging of multiple therapeutic approaches into one coordinated protocol enhances anti-tumor immune responses while managing the complexity through integrated administration strategies.
2Reliability
If tumor-associated macrophages are targeted to inhibit immune suppression, then tumor progression is suppressed, but the mechanism understanding remains incomplete
Solution Approach 1:
The patent employs agents that modulate CD11b expression and activity, which in turn affects macrophage polarization and immune suppression. By monitoring the effects of CD11b agonists on macrophage phenotype and tumor progression, the treatment creates a feedback loop that helps elucidate the molecular mechanisms while simultaneously achieving therapeutic suppression of tumor progression.
3Productivity
If CD11b agonists are used to repolarize macrophages, then tumor growth is inhibited, but the treatment specificity requirements increase
Solution Approach 1:
The patent uses agonists of CD11b expression that specifically target tumor-associated macrophages within the tumor microenvironment. By focusing the therapeutic effect on the local tumor site rather than systemically affecting all macrophages, the treatment achieves high tumor growth inhibition while maintaining precise spatial specificity. The agonists are designed to act locally on CD11b+ macrophages at the tumor boundary and within the tumor mass.
Data Source
AI summary
The present invention is based on the finding that CD11b signaling inhibits immune suppression, modulates neovascularization and promotes anti-tumor immune responses in models of murine and human cancer. As such, provided herein are methods of treating cancer using an antibody, protein or small molecule that modulates CD11b activity or expression. Also provided are methods of identifying cancer that is amenable to such treatment and/or increasing susceptibility of cancer cells to treatment with a chemotherapeutic agent.