ILT3xCD3 Bispecific Agents Targeting Tumor Evasion
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Solution Overview
Problem
There is a need for more effective molecules to enhance the immune system's ability to target and eliminate cancer cells, as many cancerous cells have developed mechanisms to evade immune surveillance.
Innovation Solution
Development of ILT3×CD3 binding agents comprising a first binding region that binds to human ILT3 and a second binding region that binds to human CD3, with the CD3 binding region comprising an anti-CD3 scFv, and optionally an Fc region, where the binding affinity of the first binding region for ILT3 is higher than that of the second binding region for CD3, and the polypeptides may have engineered cavities and protuberances for dimerization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional immunotherapy agents are used, then the immune system is activated to attack cancer cells, but cancerous cells have developed mechanisms to evade immune surveillance, reducing effectiveness
Solution Approach 1:
The binding agent is divided into distinct functional modules: an ILT3 binding region (first binding region) and a CD3 binding region (second binding region). This segmentation allows the agent to simultaneously engage both the tumor cell via ILT3 and the T cell via CD3, creating a targeted immune response that overcomes evasion mechanisms by requiring dual binding for activation.
Solution Approach 2:
The binding agent acts as an intermediary molecule that bridges the T cell and the tumor cell. By containing both ILT3 and CD3 binding regions in a single molecule, it mediates the interaction between these two cells, directing the T cell's cytotoxic activity specifically toward ILT3-expressing tumor cells while sparing normal cells.
2Measurement precision
If binding affinity of the first binding region for ILT3 is increased to enhance tumor targeting, then specificity improves, but the overall molecule complexity increases
Solution Approach 1:
The binding agent is divided into distinct functional modules: an ILT3 binding region (first binding region) and a CD3 binding region (second binding region). This segmentation allows the agent to simultaneously engage both the tumor cell via ILT3 and the T cell via CD3, creating a targeted immune response that overcomes evasion mechanisms by requiring dual binding for activation.
Solution Approach 2:
The binding agent performs multiple functions within a single molecular structure: it binds to ILT3 on tumor cells, binds to CD3 on T cells, and facilitates T cell activation and cytotoxicity. This multi-functionality is achieved by incorporating both binding regions into one agent, reducing the need for multiple separate molecules.
3Productivity
If T cells are activated to kill cancer cells, then tumor elimination increases, but normal hematopoietic stem cells may be affected
Solution Approach 1:
The binding agent exhibits local quality by targeting specifically to ILT3-expressing cells. The ILT3 binding region is designed to recognize and bind only to ILT3, which is selectively expressed on certain tumor cells but not on normal hematopoietic stem cells. This localized targeting ensures that T cell activation and cytotoxicity are directed specifically at the tumor cells expressing ILT3, sparing normal cells that lack this target antigen.
Data Source
AI summary
The present disclosure relates to ILT3×CD3 binding agents, compositions comprising thereof, and methods of use thereof. The present disclosure also relates to polynucleotides and vectors encoding such ILT3×CD 3 binding agents.