Integrin Agonist Compounds for Enhancing Cell Homing
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Solution Overview
Problem
There is a need for compounds that enhance vaccine efficacies, adoptive cell therapies, antitumor therapies, and therapeutic antibody therapies by promoting integrin-ligand interactions, cell homing, migration, and infiltration, which existing technologies have not adequately addressed.
Innovation Solution
Small molecule integrin agonists or integrin activating compounds that interact with cell surface integrins, converting them from an inactive to an active state, facilitating efficient interactions with ligands and enhancing therapeutic activities, including vaccine efficacies and antitumor therapies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If integrin agonists are used to enhance therapeutic activities, then vaccine efficacy and antitumor therapy are improved, but the complexity of the therapeutic regimen increases
Solution Approach 1:
The patent employs integrin agonists as intermediary compounds that mediate between therapeutic agents and target cells. These agonists bind to integrins on cell surfaces, facilitating interactions between therapeutic antibodies, vaccines, and tumor cells, thereby enhancing therapeutic efficacy without requiring complex multi-drug regimens
Solution Approach 2:
The integrin agonists described have broad applicability across multiple therapeutic areas including cancer immunotherapy, vaccine development, and cell-based therapies. The same class of compounds can enhance different therapeutic modalities by universally activating integrin-mediated cell adhesion and migration pathways
2Productivity
If integrin agonists are administered to enhance cell homing and migration, then therapeutic activity is improved, but potential off-target effects and safety concerns increase
Solution Approach 1:
The patent employs integrin agonists with specific molecular structures that target particular integrin subtypes (e.g., α4β1, αVβ3) expressed on specific cell types. This specificity ensures that cell homing and migration are enhanced only at the desired therapeutic site rather than systemically, reducing off-target effects
Solution Approach 2:
The integrin agonists are administered prior to or concurrent with therapeutic cells, pre-activating integrins on target tissues to create a favorable environment for cell homing and infiltration. This timing strategy ensures that the therapeutic cells encounter activated integrins rather than encountering resistance from inactive integrin states
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
These compounds effectively transition integrins to an active state, enhancing vaccine and antitumor therapies by improving integrin-ligand interactions, cell homing, and therapeutic antibody activities, thereby increasing the efficacy of treatments involving integrins.
Implementation Method 1
at least one moiety that protonates at biological pHs or bears a charge with associated counterion
Data Source
AI summary
Small molecule integrin agonists or integrin activating compounds including at least one di-alkylaryl amine end group and at least one alkyl or alkenoxy linking group including at least one protonatable moiety, wherein the compounds enhance vaccine efficacies, enhance adoptive cell therapy efficacies, enhance immunotherapy efficacies, enhance therapeutic antibody therapy efficacies, enhance checkpoint inhibitor therapy efficacies, enhance effector cell therapy efficacies, and enhanced cell based transplant efficacies and wherein at protonatable moiety either protonate at biological pHs or bears a charge with associated pharmaceutically acceptable counterion making the compound water soluble to improve bioavailability and methods for making and using same.