Trispecific Binding Proteins for Targeted T Cell Activation
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Solution Overview
Problem
Current methods for selectively destroying individual cells or specific cell types, such as in cancer therapy, are not efficient in specifically targeting tumor cells while sparing healthy cells.
Innovation Solution
Development of trispecific antigen-binding proteins that comprise a domain specifically binding to human CD3, a half-life extension domain, and a domain specifically binding to a target antigen, allowing for specific targeting and activation of cytotoxic T cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional methods are used for selective cell destruction, then healthy cells are spared, but tumor cell targeting efficiency is insufficient
Solution Approach 1:
The antibody is divided into multiple functional domains: a target antigen-binding domain for specific tumor cell recognition, a CD3-binding domain for T cell engagement, and a half-life extension domain for prolonged circulation. This segmentation allows each domain to perform its specialized function optimally
Solution Approach 2:
The trispecific antigen-binding protein performs multiple functions simultaneously: it targets tumor cells via the antigen-binding domain, activates cytotoxic T cells through CD3 engagement, and extends its own half-life through the half-life extension domain. This multi-functionality resolves the contradiction by achieving both high specificity and high efficiency in a single molecule
2Length of moving object
If small binding proteins are used, then tissue penetration is improved, but half-life is reduced
Solution Approach 1:
The binding protein is constructed as a composite molecule combining different functional domains with distinct properties. The small size domains (antigen-binding and CD3-binding) provide tissue penetration, while the incorporated half-life extension domain (such as Fc or albumin-binding domain) provides prolonged circulation time. This composite structure resolves the size-half-life tradeoff
Data Source
AI summary
Provided herein are trispecific antigen-binding proteins comprising a domain binding to CD3, a half-life extension domain, and a domain binding to a target antigen. Also provided are pharmaceutical compositions thereof, as well as nucleic acids, recombinant expression vectors and host cells for making such trispecific antigen-binding proteins. Also disclosed are methods of using the disclosed trispecific antigen-binding proteins in the prevention, and/or treatment diseases, conditions and disorders.