Anti-ROR1 Antibody CDR Engineering for Cross-Species Binding
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Solution Overview
Problem
Current anti-ROR1 antibodies have limitations in cross-reactivity and binding efficiency, particularly in recognizing human, monkey, and mouse ROR1, which affects their efficacy in cancer treatment and drug development.
Innovation Solution
Development of a specific antibody or antigen-binding fragment with defined heavy and light chain complementarity determining regions (CDRs) that can recognize human ROR1 and show cross-reactivity with monkey and mouse ROR1, including specific sequences for CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3, enabling effective binding to ROR1 across species.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If existing anti-ROR1 antibodies are used, then cancer treatment efficacy is achieved, but cross-reactivity to human, monkey, and mouse ROR1 is limited
Solution Approach 1:
The patent modifies the antibody's complementarity determining regions (CDRs) to change its binding parameters, enabling cross-species recognition while maintaining high affinity. Specific amino acid substitutions in CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 were made to broaden specificity across human, monkey, and mouse ROR1 variants.
Solution Approach 2:
The engineered antibody is designed to perform multiple functions: it binds to human, monkey, and mouse ROR1 with comparable efficiency, making it universally applicable for cancer treatment across different species and for drug development purposes requiring cross-species validation.
2Reliability
If ROR1 expression is inhibited in cancer cells, then metastasis is reduced and survival time is increased, but current antibodies have limited binding efficiency
Solution Approach 1:
The antibody's binding parameters were optimized through CDR engineering to achieve higher affinity and specificity for ROR1. This enhanced binding efficiency directly improves the antibody's ability to inhibit cancer cell proliferation and induce apoptosis, thereby increasing treatment efficacy.
3Adaptability or versatility
If a new antibody with defined CDR sequences is developed, then cross-reactivity is improved, but development complexity increases
Solution Approach 1:
The antibody development process was segmented into modular CDR regions (CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, CDRL3), allowing independent optimization of each region's sequence to achieve cross-reactivity without redesigning the entire antibody structure.
Solution Approach 2:
Specific amino acid sequences in the CDR regions were systematically modified to achieve the desired cross-reactivity profile. This targeted parameter change approach allowed precision engineering of the antibody's binding properties without introducing unnecessary structural complexity.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The antibody effectively inhibits cancer growth by specifically binding to ROR1, demonstrating significant tumor inhibition in mouse xenograft models and inducing apoptosis in cancer cells, thus offering a promising therapeutic agent for various cancers.
Implementation Method 1
an antibody or antigen-binding fragment (1) that specifically binds to an extracellular domain of ROR1
Data Source
AI summary
The present invention discloses an anti-ROR1 antibody specifically recognizing human and mouse ROR1. The monoclonal antibody can be usefully used for cancer targeting treatment including detection of various cancer expressing ROR1 through specific binding, and drug delivery to specific cancer, etc. as well as a cancer therapeutic agent, by inhibiting tumors.