FAP-Binding Agents for Local CAF Reprogramming and Immune Recruitment
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Solution Overview
Problem
There is a need for improved therapies to target and modify the functions of aberrant fibroblasts, particularly cancer-associated fibroblasts (CAFs), to treat diseases such as cancer and fibrotic diseases.
Innovation Solution
Development of fibroblast binding agents, including FAP targeting moieties like single-domain antibodies (VHHs), which can alter or polarize the disease microenvironment by recruiting immune cells and delivering signaling agents to modulate fibroblast activity, thereby targeting FAP and other antigens or receptors on fibroblast cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional therapies are used to target aberrant fibroblasts, then treatment coverage is limited, but the complexity of the disease microenvironment remains unaddressed
Solution Approach 1:
The fibroblast binding agent is designed as a multi-functional platform that can simultaneously perform targeting, signaling delivery, and immune cell recruitment. The agent includes a FAP targeting moiety, a signaling agent domain, and optional additional targeting moieties, allowing it to address multiple aspects of the disease microenvironment through a single therapeutic intervention.
2Reliability
If fibroblast binding agents deliver signaling agents to modulate fibroblast activity, then therapeutic effect is enhanced, but the risk of off-target effects increases
Solution Approach 1:
The signaling agent is delivered locally to fibroblasts through the fibroblast binding agent that specifically targets FAP-expressing cells. This localized delivery ensures that the signaling agent acts primarily on the intended fibroblast population in the disease microenvironment, minimizing off-target effects on other cell types or tissues.
Solution Approach 2:
The fibroblast binding agent serves as an intermediary carrier that bridges the signaling agent and the fibroblast target. This mediator approach allows controlled delivery of the signaling agent to the specific cellular target, reducing the risk of systemic or off-target effects while maintaining therapeutic efficacy.
3Measurement precision
If additional targeting moieties are included to bind other targets on fibroblast cells, then specificity is improved, but the device complexity increases
Solution Approach 1:
Multiple targeting moieties are merged into a single fibroblast binding agent construct, allowing simultaneous targeting of FAP and other fibroblast-specific antigens or receptors. This combined approach enhances specificity for fibroblast cells while maintaining a unified agent structure that can be administered as a single therapeutic product.
Data Source
AI summary
The present invention relates, in part, to agents that bind fibroblast activation protein (FAP) and their use as diagnostic and therapeutic agents. The present invention further relates to pharmaceutical compositions comprising the FAP binding agents and their use in the treatment of various diseases.