Clec4C-Targeted Chimeric Proteins for pDC Immune Modulation

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Solution Overview

Problem

Existing therapies are inadequate for modifying dendritic cell functions to effectively treat diseases such as cancer and autoimmune diseases like multiple sclerosis, particularly in targeting plasmacytoid dendritic cells (pDCs) to modulate immune responses.

Innovation Solution

Development of chimeric proteins and chimeric protein complexes with targeting moieties that bind to Clec4C on pDCs, incorporating modified signaling agents to recruit and modulate pDCs, thereby facilitating antigen presentation and immune response modulation without systemic adverse effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing therapies are used to modify dendritic cell functions, then some immune modulation effect is achieved, but the therapies are inadequate for effectively treating cancer and autoimmune diseases

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidability to target specific DC subtypes

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent segments dendritic cells into distinct subtypes (cDC1, cDC2, pDC) based on their functional characteristics and surface markers. By developing agents that specifically target each subtype through unique markers (XCR1 for cDC1, CLEC9A for cDC2, CLEC4C for pDC), the therapy achieves precise subtype-specific modulation, resolving the contradiction between therapeutic effectiveness and ability to target specific DC subtypes.

Inventive Principle:

Principle #1Segmentation

2Productivity

If pDCs are recruited to a site of interest using Clec4C binding agents, then pDC recruitment is enhanced, but Clec4C signaling function may be blocked

Engineering Contradiction:

ImprovepDC recruitment efficiencyVSAvoidClec4C signaling function

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent applies local quality by designing binding agents with specific properties for different purposes. Some agents are designed to bind Clec4C with high affinity for recruitment purposes, while others are designed to bind with lower affinity or at different epitopes to preserve signaling function. This localized differentiation in binding agent properties allows simultaneous achievement of efficient recruitment and preserved signaling function.

Inventive Principle:

Principle #3Local quality

3Reliability

If chimeric proteins with modified signaling agents are used, then precise targeting and modulation of pDCs is achieved, but device complexity increases

Engineering Contradiction:

Improvetargeting precisionVSAvoidchimeric protein structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent merges multiple functional components into single chimeric protein molecules. Each chimeric protein combines a targeting moiety (antibody or antigen-binding fragment) with a signaling agent (cytokine or chemokine), creating a bifunctional molecule that can simultaneously target specific DC subtypes and modulate their function. This merging reduces the need for multiple separate agents and simplifies the overall therapeutic regimen despite the increased molecular complexity.

Inventive Principle:

Principle #5Merging (Combining)

Data Source

PatentUS20260109748A1Modulation of dendritic cell lineages

Publication Date: 2026.04.23 ORIONIS BIOSCIENCES BV

AI summary

The present invention relates, in part, to agents, chimeric proteins and chimeric protein complexes that bind a plasmacytoid dendritic cell (pDC), e.g. Clec4C and their use as diagnostic and therapeutic agents. The present Invention further relates to pharmaceutical compositions comprising the pDC, e.g. Clec4C, binding agents, chimeric proteins, or chimeric protein complexes and their use in the treatment of various diseases, including autoimmune diseases.