Humanized ICOS Antibody T Cell Activation
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Solution Overview
Problem
Current cancer treatments lack effective T cell proliferation inducing molecules, limiting the immunotherapeutic options for enhancing anti-tumor responses.
Innovation Solution
Development of ICOS binding proteins, specifically humanized monoclonal antibodies with defined CDR sequences, that bind to human ICOS, stimulating cytokine production and T cell proliferation, and potentially used in combination with other immunomodulatory antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current cancer treatments are used, then existing therapeutic options are available, but T cell proliferation inducing capability is insufficient
Solution Approach 1:
Instead of using ICOS-L (the natural ligand) to activate ICOS, the patent uses a humanized monoclonal antibody (H2L5) that binds to ICOS and mimics its activation. This inversion of the natural binding approach allows for controlled agonist activity with potentially improved safety and efficacy profiles compared to natural ligand activation.
Solution Approach 2:
The patent employs a humanized antibody with specific CDR sequences that are engineered to optimize binding affinity and agonist activity to ICOS. By modifying the antibody's structural parameters (CDR regions), the treatment achieves enhanced T cell proliferation inducing capability while maintaining immunotherapeutic versatility.
2Productivity
If ICOS is activated to enhance anti-tumor T cell function, then T cell proliferation increases, but the mechanism for controlled activation needs to be established
Solution Approach 1:
The humanized monoclonal antibody H2L5 serves as an intermediary between the therapeutic agent and the ICOS receptor. Rather than directly activating ICOS with its natural ligand ICOS-L, the antibody mediates activation in a controlled manner, allowing for regulated T cell proliferation while maintaining reliability and controllability of the activation mechanism.
Solution Approach 2:
The use of a humanized antibody allows for potential feedback control mechanisms where the antibody's binding and activation of ICOS can be monitored and regulated. This enables controlled activation where T cell proliferation can be modulated based on therapeutic needs, improving the reliability of the activation mechanism.
Data Source
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AI summary
The present invention relates to an ICOS binding protein or antigen binding portion thereof that is an agonist to human ICOS and does not induce complement, ADCC, or CDC when placed in contact with a T cell in vivo and methods of treating cancer, infectious disease and/or sepsis with said ICOS binding protein or antigen binding portion thereof. Further the ICOS binding proteins or antigen binding portions thereof of the present invention are capable of activating a T cell when placed in contact with said T cell; stimulating T cell proliferation when placed in contact with said T cell and/or inducing cytokine production when placed in contact with said T cell. The present invention relates to ICOS binding proteins or antigen binding portions thereof comprising one or more of: SEQ ID NO:1; SEQ ID NO:2; SEQ ID NO:3; SEQ ID NO:4; SEQ ID NO:5; and/or SEQ ID NO:6.