Clec9a Binding Agents for Targeted Dendritic Cell Recruitment
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Solution Overview
Problem
There is a need for improved therapies for diseases such as cancer and multiple sclerosis by modifying dendritic cell functions, as derailed dendritic cell functions contribute to immune evasion by cancer cells and autoimmune diseases.
Innovation Solution
Development of Clec9A binding agents that specifically bind to Clec9A without functionally modulating it, allowing for the recruitment of Clec9A-expressing cells to sites of interest while maintaining their signaling capability. These agents can include targeting moieties like single domain antibodies and signaling agents like interferons, interleukins, or tumor necrosis factors, which may be modified to attenuate activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If Clec9A binding agents are used to recruit dendritic cells to sites of interest, then immune cell recruitment is improved, but functional modulation or neutralization of Clec9A may occur
Solution Approach 1:
The binding agent is divided into separate functional domains: a targeting moiety (such as a single domain antibody) that binds to Clec9A for recruitment purposes, and a signaling agent component that can be independently controlled. This segmentation allows the recruitment function to be activated without necessarily activating or inhibiting the signaling function, resolving the contradiction between recruitment effectiveness and signaling capability preservation.
Solution Approach 2:
The patent introduces an intermediary binding agent that acts as a mediator between the dendritic cell and the site of interest. This intermediary can be designed to bind to Clec9A and facilitate recruitment while maintaining the ability to control signaling outcomes, thereby resolving the contradiction between effective recruitment and preserving signaling capability.
2Productivity
If dendritic cell functions are modified to treat cancer, then antitumor immune response is improved, but autoimmunity may be triggered
Solution Approach 1:
The binding agent is designed to exhibit local quality differences through its targeting moiety that specifically recognizes Clec9A on dendritic cells. This localized recognition allows the agent to modulate dendritic cell function specifically at the tumor site without systemically affecting other immune cells, thereby generating antitumor response while minimizing the risk of triggering autoimmunity.
Solution Approach 2:
The patent employs parameter changes by using signaling agents that can be modified to attenuate their activity. This allows fine-tuning of the immune response parameters to achieve sufficient antitumor activity while staying below the threshold that would trigger autoimmune responses, thus resolving the contradiction between therapeutic effectiveness and safety.
3Productivity
If Clec9A binding agents bind to Clec9A, then dendritic cell recruitment is enhanced, but Clec9A signaling may be reduced or eliminated
Solution Approach 1:
The binding agent system is designed with dynamic characteristics where the binding to Clec9A can be reversible and context-dependent. The targeting moiety can bind to Clec9A to facilitate recruitment, but the interaction can be dynamically adjusted to maintain signaling capability when needed, thereby resolving the contradiction between recruitment enhancement and signaling preservation.
Data Source
AI summary
The present invention relates, in part, to agents that bind Clec9A and their use as diagnostic and therapeutic agents. The present invention further relates to pharmaceutical compositions comprising the Clec9A binding agents and their use in the treatment of various diseases.