TAM-Binding Molecules for Macrophage Repolarization in Cancer
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Solution Overview
Problem
Existing technologies have difficulty in effectively targeting and eliminating tumor-associated macrophages (TAMs) within the tumor microenvironment, which are responsible for creating an immunosuppressive environment that hinders the immune system's ability to recognize and eliminate cancer cells.
Innovation Solution
Development of molecules, such as CRV, that specifically bind to tumor-associated macrophages (TAMs) by targeting the retinoid X receptor beta (RXRB) on their surface, allowing for the delivery of therapeutic or diagnostic agents to modulate their activity or facilitate their detection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional therapies are used to target tumor cells, then tumor cell elimination may be achieved, but the immunosuppressive tumor microenvironment created by TAMs remains unchanged, preventing effective immune recognition and elimination of cancer cells
Solution Approach 1:
The patent uses binding molecules (antibodies, peptides, or small molecules) as intermediaries to specifically target TAMs in the tumor microenvironment. These molecules bind to TAM surface markers (such as CD163, CD206, or CXCR4) and deliver therapeutic payloads including cytotoxic agents, immunomodulators, or repolarization factors. This intermediary approach allows selective modification of TAM function without affecting other cell types, thereby overcoming the immunosuppressive barrier while maintaining tumor cell elimination capabilities
Solution Approach 2:
The patent employs therapeutic agents that change the functional parameters of TAMs by repolarizing them from the M2 (immunosuppressive) phenotype to the M1 (pro-inflammatory and anti-tumor) phenotype. This parameter change is achieved through delivery of specific molecules such as interferon-gamma, lipopolysaccharide, or other immunomodulators that alter TAM gene expression profiles, cytokine production, and surface marker expression, transforming their function from tumor-promoting to tumor-fighting
2Adaptability or versatility
If therapies target the tumor microenvironment to reduce immunosuppression, then immune response may be enhanced, but specificity in targeting TAMs versus other immune cells becomes difficult to achieve
Solution Approach 1:
The patent segments the immune system by developing binding molecules that specifically recognize and bind to TAM-associated surface markers (such as CD163, CD206, CXCR4, or other TAM-enriched markers) while not binding to or having minimal binding to other immune cell markers. This segmentation allows selective targeting of TAMs within the heterogeneous tumor microenvironment, enabling precise modulation of TAM function without affecting T cells, B cells, natural killer cells, or other immune cell populations
Solution Approach 2:
The patent uses highly specific binding molecules (monoclonal antibodies, peptide ligands, or small molecules with high affinity and selectivity) as intermediaries that act as molecular guides to deliver therapeutic payloads exclusively to TAMs. These intermediary molecules provide spatial and cellular specificity by recognizing unique TAM surface features, ensuring that therapeutic effects are concentrated on TAMs while sparing other immune cells
Data Source
AI summary
Provided herein are binding molecules to tumor associated macrophages and associated methods for the treatment and detection of cancer.