Anti-ILT2 Antibodies for Reversing Tumor Immune Suppression
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Solution Overview
Problem
ILT2, expressed on immune cells, inhibits effective immune response against cancer, acting as a roadblock to oncolytic immune therapy, particularly in HLA-G1-expressing malignancies, necessitating treatment modalities that circumvent its suppressive function.
Innovation Solution
Development of monoclonal antibodies and antigen binding fragments that specifically target ILT2, inhibiting its immune suppression and enhancing PD-1/PD-L1 immunotherapy by increasing NK cell cytotoxicity, T cell cytotoxicity/proliferation, macrophage phagocytosis, and dendritic cell activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If oncolytic immune therapy is used to treat cancer, then immune response is activated, but ILT2-mediated immune suppression blocks the effectiveness of the therapy
Solution Approach 1:
The patent introduces an intermediary substance (anti-ILT2 antibody or inhibitory compound) that mediates between the immune system and the cancer cells. This intermediary blocks the harmful interaction between ILT2 and HLA-G1, allowing the immune therapy to function effectively without being suppressed by the ILT2 pathway.
Solution Approach 2:
The patent applies preliminary anti-action by administering an agent that specifically inhibits ILT2 function before or during immune therapy. This preliminary blockade prevents the suppressive effect from taking hold, ensuring that subsequent immune responses are not dampened by the ILT2-HLA-G1 axis.
2Productivity
If ILT2 expression is present in the tumor microenvironment, then immune suppression occurs, but eliminating ILT2 function is needed to improve clinical response
Solution Approach 1:
The patent extracts or removes the harmful function of ILT2 from the tumor microenvironment by using specific inhibitors that bind to ILT2 and block its suppressive activity. This extraction of the harmful element allows the immune system to function normally without the dampening effect of ILT2.
Solution Approach 2:
The patent converts the harmful presence of ILT2 into a benefit by using it as a therapeutic target. By developing agents that specifically inhibit ILT2, the previously harmful suppressive pathway becomes a point of intervention that, when blocked, enhances immune response and improves clinical outcomes.
3Reliability
If HLA-G1 is expressed on cancer cells, then immune evasion is enhanced, but blocking the ILT2-HLA-G1 axis is necessary to restore immune surveillance
Solution Approach 1:
The patent uses an intermediary agent (anti-ILT2 antibody or inhibitor) that specifically targets the ILT2 receptor rather than HLA-G1 directly. This intermediary blocks the interaction between ILT2 and HLA-G1, preventing immune evasion without needing to eliminate HLA-G1 expression itself.
Solution Approach 2:
Instead of trying to block HLA-G1 expression on cancer cells (which would be difficult), the patent inverts the approach by blocking the receptor (ILT2) on immune cells. This reverse strategy achieves the same functional outcome - preventing the suppressive signal - but is more feasible and effective.
Data Source
AI summary
The present invention provides monoclonal antibodies, or antigen-binding portions thereof, against ILT2, as well as pharmaceutical compositions comprising same and methods of producing same. Also provided are methods of treating cancer comprising administering the antibodies or compositions of the invention. Methods of treating cancer, combination treatments, and patient selection are also provided.