ROR1 Antigen-Binding Proteins for Selective Tumor Cell Killing
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Solution Overview
Problem
Current treatments for ROR1-expressing tumors lack effective targeted therapies, as ROR1 is lowly expressed in normal tissues but highly expressed in various blood and solid tumors, making it a promising target for tumor-specific markers and treatments.
Innovation Solution
Development of antigen-binding proteins, including single-domain antibodies and chimeric antigen receptors, specifically targeting ROR1 to enhance tumor-killing effects by binding to ROR1 on tumor cell surfaces.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments are used for ROR1-expressing tumors, then general tumor treatment approaches are applied, but they lack effective targeted therapy and fail to exploit the specific expression pattern of ROR1
Solution Approach 1:
The patent applies local quality by designing antigen-binding proteins with specific affinity for ROR1-expressing tumor cells. The CDR regions are engineered to recognize and bind specifically to ROR1 antigen on the surface of blood and solid tumors, while normal tissues expressing low or no ROR1 remain unaffected. This localized targeting approach enables selective tumor cell recognition and destruction without compromising healthy tissues.
Solution Approach 2:
The patent utilizes parameter changes by modifying the binding affinity and specificity parameters of the antigen-binding proteins. Through optimization of CDR amino acid sequences, the proteins achieve high affinity binding to ROR1-positive tumor cells while maintaining selectivity. The binding constant and specificity parameters are tuned to maximize tumor cell targeting effectiveness.
2Strength
If antigen-binding proteins are designed to bind strongly to ROR1 on tumor cells, then tumor-killing effect is enhanced, but specificity to normal tissues must be maintained
Solution Approach 1:
The antigen-binding proteins exhibit local quality by demonstrating high binding strength specifically at tumor cell surfaces expressing ROR1, while showing minimal to no binding to normal tissues. The CDR regions are designed to recognize unique epitopes on ROR1 that are either absent or present at very low levels in normal tissues, thereby concentrating the strong binding effect locally at tumor sites and avoiding off-target effects.
Solution Approach 2:
The antigen-binding proteins serve as intermediaries that bridge the gap between the immune system and ROR1-expressing tumor cells. These proteins specifically bind to ROR1 on tumor cells, recruiting immune effector cells through Fc region interactions or direct immune activation, thereby mediating tumor cell destruction while maintaining specificity through the unique antigen-binding properties of the CDR regions.
Data Source
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AI summary
Provided are an isolated antigen-binding protein, a preparation method therefor, and use thereof. The isolated antigen-binding protein can bind to a receptor tyrosine kinase-like orphan receptor 1 (ROR1). The antigen protein comprises CDR1, CDR2, and CDR3.