Chimeric Receptor Merging Binding and Signaling Domains
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Solution Overview
Problem
Current cancer immunotherapy strategies face limitations in effectively targeting and eliminating cancer cells while sparing healthy tissues, as existing immune receptors lack efficient mechanisms to diversify ligand-binding capabilities without compromising signaling functions.
Innovation Solution
Development of chimeric receptors comprising an extracellular binding domain and a heterologous amino acid sequence that recruits a co-receptor with an intracellular signaling domain, allowing for targeted immune responses against pathologic cells by forming a protein complex that transmits activation signals upon binding to specific ligands or receptors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If immune receptors use multi-subunit complexes with separate ligand-binding and signaling subunits, then ligand-binding diversity can be achieved through gene mutation and diversification, but the receptor structure becomes more complex requiring assembly of multiple subunits
Solution Approach 1:
The patent combines the ligand-binding domain and signaling domain into a single chimeric receptor polypeptide chain, eliminating the need for separate subunit assembly while maintaining the ability to recognize diverse ligands through the extracellular binding domain and transmit signals through the intracellular signaling domain
Solution Approach 2:
The chimeric receptor is constructed as a composite protein molecule containing both the extracellular ligand-binding domain and the intracellular signaling domain in a single polypeptide chain, allowing functional integration without structural complexity of multi-subunit assembly
2Reliability
If a conserved signaling subunit is shared by receptors with different ligand-binding specificities, then signaling function is preserved, but the receptor requires assembly with additional ligand-binding subunits increasing complexity
Solution Approach 1:
The patent merges the conserved signaling domain with the ligand-binding domain into a single chimeric receptor molecule, preserving reliable signal transduction through the intracellular domain while eliminating the need for separate assembly with additional subunits
3Adaptability or versatility
If existing immune receptors are used for cancer targeting, then immune cells can recognize cancer cells, but the ability to specifically eliminate cancer cells while sparing healthy tissues is limited
Solution Approach 1:
The patent employs chimeric receptors with extracellular domains that specifically recognize cancer-associated ligands or receptors, enabling localized and selective targeting of cancer cells while preserving healthy tissues through targeted ligand-binding specificity in the extracellular domain
Data Source
AI summary
Chimeric receptors are provided. Accordingly, there is provided a chimeric receptor comprising an extracellular binding domain and a heterologous amino acid sequence capable of recruiting a co-receptor comprising an intracellular signaling domain, such that upon binding of the extracellular binding domain to its target the signaling is transmitted in a cell expressing the chimeric receptor and the co-receptor. Also provided are protein complexes comprising the receptors, cells expressing same and uses thereof.