Multispecific Molecules for Targeted Cancer Therapy
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Solution Overview
Problem
Current cancer therapies often face challenges in effectively targeting cancer cells while minimizing systemic toxicity, as existing immune therapeutics can have broad immune activation leading to unwanted side effects.
Innovation Solution
Development of multispecific or multifunctional molecules that combine a tumor-targeting moiety with an immune cell engager, cytokine molecule, or stromal modifying moiety to enhance localized immune response against cancer cells, reducing systemic toxicity by balancing affinities to ensure higher binding to tumor and stroma cells compared to immune effector cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If broad immune activation is used to enhance anti-tumor immunity, then immune response effectiveness is improved, but systemic toxicity increases
Solution Approach 1:
The multispecific molecule is designed to concentrate immune activation locally at the tumor site through dual targeting: one arm binds tumor-specific antigens while the other arm recruits immune cells. This localized immune engagement enhances anti-tumor immunity without triggering widespread systemic immune activation, thereby reducing systemic toxicity while maintaining therapeutic effectiveness.
Solution Approach 2:
The multispecific molecule acts as an intermediary that bridges tumor cells and immune cells through its dual binding capabilities. By mediating the interaction between tumor antigens and immune cell receptors, it enables targeted immune recruitment to the tumor microenvironment, achieving effective local immune response while avoiding unnecessary systemic immune activation and associated toxicities.
2Reliability
If high affinity binding to immune effector cells is increased to enhance immune engagement, then immune cell activation is improved, but off-target binding increases
Solution Approach 1:
The molecule employs differential affinity design where the tumor-targeting arm has high affinity for tumor-specific antigens, while the immune cell-engaging arm has optimized but lower affinity for immune cell receptors. This ensures that immune cell binding only occurs when the molecule is already anchored to tumor cells, providing spatial control over immune engagement and preventing off-target binding to healthy tissues.
Solution Approach 2:
The patent utilizes affinity maturation and engineering to precisely tune the binding parameters of each arm of the multispecific molecule. By independently optimizing the dissociation constants (Kd) of the tumor antigen binding and immune cell receptor binding, the molecule achieves the desired balance: sufficient affinity for effective immune engagement at the tumor site, while maintaining low enough affinity to prevent non-specific binding to off-target cells.
Data Source
AI summary
Multispecific molecules that include i) a tumor-targeting moiety; and one, two or all of: (ii) an immune cell engager (e.g., chosen from an NK cell engager, a T cell engager, a B cell engager, a dendritic cell engager, or a macrophage cell engager); (iii) a cytokine molecule; and/or (iv) a stromal modifying moiety are disclosed. Additionally disclosed are nucleic acids encoding the same, methods of producing the aforesaid molecules, and methods of treating a cancer using the aforesaid molecules.