Multi-Antigen TCR Recognition to Reduce Cancer Immune Escape
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Solution Overview
Problem
Existing cancer therapies often rely on single TCRs that target a single cancer antigen, making them susceptible to immune escape by cancer cells, and there is a need for more effective and safer immunotherapy approaches that can target multiple cancer antigens simultaneously.
Innovation Solution
Development of anti-cancer TCRs and T-cells that recognize multiple distinct cancer antigens via shared epitope sequences, specifically targeting Melan A, BST2, and IMP2 polypeptides with the x-x-x-A/G-I/L-G-I-x-x-x recognition motif, and their delivery via vectors and ex vivo processes to modify immune cells for cancer treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If a single TCR targets a single cancer antigen, then the therapy is simpler to design and implement, but cancer cells can easily evade immune detection through immune escape
Solution Approach 1:
The patent applies universality by designing a single TCR that can recognize multiple different cancer antigens (Melan A, BST2, IMP2) through their shared epitope sequences. This multi-functional TCR provides broad cancer coverage while maintaining a relatively simple single-receptor design, resolving the contradiction between reliability against immune escape and device complexity
Solution Approach 2:
The patent changes the recognition parameter of the TCR from antigen-specific to motif-specific (x-x-x-A/G-I/L-G-I-x-x-x). By targeting the conserved peptide motif rather than entire antigen sequences, the TCR can bind multiple antigens presenting this motif, thereby improving reliability against immune escape without requiring multiple different TCRs
2Reliability
If multiple TCRs are used to target multiple cancer antigens, then immune escape is reduced, but the therapy becomes more complex and harder to implement
Solution Approach 1:
The patent creates a universal TCR that functions against multiple cancer types by recognizing the conserved x-x-x-A/G-I/L-G-I-x-x-x motif across different antigens. This single multi-functional TCR replaces the need for multiple separate TCRs, maintaining reliability against immune evasion while significantly improving ease of operation and therapeutic implementation
3Adaptability or versatility
If conventional single-epitope T-cell recognition is used, then the T-cell design is simpler, but the recognition capability against diverse cancer cells is limited
Solution Approach 1:
The patent changes the recognition parameter from entire antigen specificity to conserved motif specificity (x-x-x-A/G-I/L-G-I-x-x-x). This parameter change enables the TCR to recognize diverse cancer cells expressing different antigens that all contain this motif, greatly improving adaptability while keeping the TCR design relatively simple through focused motif recognition rather than comprehensive antigen coverage
Data Source
AI summary
There is provided inter alia an isolated anti-cancer T-cell receptor (TCR), or anti-cancer binding fragment thereof, that binds to a plurality of cancer polypeptide antigens or antigenic peptide fragments thereof wherein said cancer polypeptide antigens or antigenic peptide fragments thereof are distinct from each other and are presented at the cell surface of one or more than one type of cancer cell.