ILT3 Binding Molecules for Immune Modulation
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Solution Overview
Problem
Current technologies lack effective agents to modulate immune responses by targeting Immunoglobulin-like transcript 3 (ILT3) on antigen-presenting cells, which are crucial for regulating immune activation and reducing inflammatory cytokine production and costimulatory molecule upregulation.
Innovation Solution
Development of binding molecules with high affinity for ILT3 on antigen-presenting cells, such as monocytes and dendritic cells, that downmodulate immune cell activation in vitro and are immunostimulatory in vivo, upregulating inhibitory receptors and modulating cytokine production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If binding molecules are designed to downmodulate immune cell activation in vitro, then immune responses are suppressed in vitro, but immune responses are stimulated in vivo
Solution Approach 1:
The patent applies parameter changes by modifying the binding molecule characteristics (affinity, isotype, Fc region) to achieve different functional outcomes. The binding molecules have been engineered with specific affinity ranges (Kd values) and Fc regions (e.g., IgG1, IgG2a) that enable them to function as immunostimulants in vivo while maintaining in vitro downmodulation activity, thus resolving the contradiction between in vitro suppression and in vivo stimulation effects
2Measurement precision
If binding molecules bind to ILT3 with high affinity, then immune cell activation is downmodulated, but complex immune modulation effects are achieved
Solution Approach 1:
The patent specifies precise binding affinity parameters (Kd values such as 0.9×10^-9 or less) to achieve optimal ILT3 binding. This parameter optimization allows the binding molecules to effectively downmodulate immune cell activation while maintaining manageable complexity in their mechanism of action through defined affinity ranges and specific Fc region configurations
Data Source
AI summary
The present invention provides binding molecules that specifically bind to ILT3, e.g., human ILT3 (hILT3), on antigen presenting cells, such as for example, monocytes, macrophages and dendritic cells (DC), e.g., monocyte-derived dendritic cells (MDDC). The binding molecules of the invention are characterized by binding to hILT3 with high affinity and downmodulating immune responses in vitro, e.g., downmodulating alloimmune responses; the production of inflammatory cytokines by dendritic cells, e.g., monocyte-derived dendritic cells (MDDC); the upregulation of costimulatory molecules by DC, e.g., MDDC; and/or calcium flux in monocytes. In addition, the binding molecules upregulate the expression of inhibitory receptors on dendritic cells, e.g., immature dendritic cells. Surprisingly, these same binding molecules which downmodulate immune responses in vitro, are immunostimulatory in vivo. Various aspects of the invention relate to binding molecules, and pharmaceutical compositions thereof. Methods of using the binding molecules of the invention to detect human ILT3 or to modulate human ILT3 activity, either in vitro or in vivo, are also encompassed by the invention.