Anti-SLeA Monoclonal Antibodies for High-Selectivity Glycan Binding
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Solution Overview
Problem
Current anti-glycan antibodies, such as Dinutuximab, have low affinity and specificity for tumor-associated carbohydrate antigens like Sialyl Lewis A (SLeA), limiting their clinical application in cancer treatment, despite the need for high-affinity and specific antibodies to target various cancer types.
Innovation Solution
Development of monoclonal antibodies with specific CDR sequences (SEQ ID NOs) and framework regions that enhance binding to SLeA, achieving high selectivity and specificity, allowing differentiation between SLeA and similar glycans, and promoting T-cell activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional anti-glycan antibodies are used, then they can recognize carbohydrate antigens, but they have low affinity and low specificity
Solution Approach 1:
The patent applies parameter changes by modifying the CDR sequences of the antibody to achieve high affinity and specificity. The specific CDR sequences (VH-CDR1: SEQ ID NO: 6, VH-CDR2: SEQ ID NO: 7, VH-CDR3: SEQ ID NO: 8, VL-CDR1: SEQ ID NO: 9, VL-CDR2: SEQ ID NO: 10, VL-CDR3: SEQ ID NO: 11) are optimized to bind SLeA with KD of 0.1 to 30 nM and selectivity >90%, resolving the contradiction between reliability and ease of manufacture.
Solution Approach 2:
The patent replaces conventional antibody development methods with yeast surface display (YSD) technology. This systematic approach uses Aga1p and Aga2p proteins expressed on yeast cell surfaces to present antibody fragments for selection, enabling high-throughput screening and optimization of anti-SLeA antibodies with improved affinity and specificity.
2Reliability
If antibody affinity is improved through selection methods, then binding strength increases, but differentiation between similar glycans becomes more difficult
Solution Approach 1:
The patent applies local quality by optimizing specific CDR regions (VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2, VL-CDR3) to achieve both high affinity and specificity. The localized optimization of these complementarity-determining regions enables the antibody to distinguish SLeA from SLeX while maintaining strong binding, resolving the contradiction between binding strength and differentiation capability.
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 antibodies demonstrate high affinity (KD of about 0.1 to 30 nM) and selectivity (>90%) for SLeA, showing improved cytotoxicity against cancer cells and potential for cancer treatment and diagnosis.
Implementation Method 1
several monoclonal antibodies bind Sialyl Lewis A (SLeA) glycans with higher specificity and selectivity than any know antibody to said antigen
Data Source
AI summary
The present invention discloses novel monoclonal antibodies and functional fragments thereof that specifically bind to SLeA carbohydrate antigen with high specificity and selectivity. The invention further provides compositions comprising the antibodies or fragments thereof as well as uses of the antibodies, fragments and compositions.