GD2-Binding CAR With Optimized CDR Sequences
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Solution Overview
Problem
Current treatments targeting GD2 for cancer therapy, such as antibody treatments and CAR treatments, have shown limited therapeutic efficacy, with weak cytotoxic action and incomplete cure rates in preclinical models.
Innovation Solution
A chimeric antigen receptor (CAR) comprising a GD2-binding domain with specific heavy- and light-chain complementarity-determining regions (CDRs) is developed, which enhances the binding affinity and cytotoxic activity against GD2-positive tumor cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antibody treatments or CAR treatments targeting GD2 are used, then cancer cells can be targeted, but the cytotoxic activity and therapeutic efficacy are insufficient
Solution Approach 1:
The patent applies parameter changes by optimizing the CDR sequences of the antibody to achieve higher binding affinity to GD2. Specifically, the heavy chain CDR1 sequence (SEQ ID NO: 1), CDR2 (SEQ ID NO: 2), and CDR3 (SEQ ID NO: 3), along with light chain CDR1 (SEQ ID NO: 9), CDR2 (SEQ ID NO: 10), and CDR3 (SEQ ID NO: 11), are designed to maximize binding strength and cytotoxic activity against GD2-positive tumor cells
Solution Approach 2:
The patent creates a composite antibody structure by combining specifically optimized heavy chain and light chain variable regions with engineered CDR sequences. This composite design integrates multiple functional elements (antigen binding, cytotoxic activation) into a single therapeutic molecule that overcomes the limitations of conventional treatments
2Reliability
If GD2-targeted treatments are administered, then tumor cells can be recognized, but complete cure is not achieved in preclinical models
Solution Approach 1:
The patent improves treatment effectiveness by changing the binding parameters of the antibody through optimized CDR sequences. The heavy chain CDR regions (SEQ ID NO: 1-3) and light chain CDR regions (SEQ ID NO: 9-11) are specifically engineered to enhance both binding affinity and biological activity, leading to improved tumor cell recognition and destruction that achieves complete cure in preclinical models
Data Source
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AI summary
Provided is a cancer treatment or prevention technique that molecularly targets GD2. A GD2-binding molecule includes a heavy-chain variable region containing a heavy-chain CDR1 containing the amino acid sequence represented by SEQ ID NO: 1, a heavy-chain CDR2 containing the amino acid sequence represented by SEQ ID NO: 2, and a heavy-chain CDR3 containing the amino acid sequence represented by SEQ ID NO: 3, and/or a light-chain variable region containing a light-chain CDR1 containing the amino acid sequence represented by SEQ ID NO: 9, a light-chain CDR2 containing the amino acid sequence represented by SEQ ID NO: 10, and a light-chain CDR3 containing the amino acid sequence represented by SEQ ID NO: 11.