MAGE-A4 T Cell Receptors for Rapid High-Avidity Cancer Targeting

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Solution Overview

Problem

Current adoptive cell therapy (ACT) for cancer treatment faces challenges in custom isolation and characterization of tumor-specific T cells, which are often inefficient and time-consuming, and existing technologies struggle to identify T cell clones with high avidity for tumor antigens like MAGE-A4, limiting broad clinical application.

Innovation Solution

Development of isolated T cell receptors (TCRs) specifically recognizing the MAGE-A4 antigen, particularly in its HLA-A2 bound form, with optimized CDR sequences for enhanced specificity and avidity, and potential modifications for stability and therapeutic integration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If custom isolation and characterization of tumor-specific T cells is performed for each patient, then tumor-specific T cell therapy can be tailored to individual patients, but the process becomes time-consuming and difficult

Engineering Contradiction:

Improvepatient-specific tumor-specific T cell therapyVSAvoidtime-consuming isolation and characterization process

Core Design Contradiction:

Adaptability or versatilityVSLoss of time

Solution Approach 1:

The patent identifies and characterizes tumor-specific T cell clones in advance during the development phase, creating a library of pre-characterized TCRs that can be rapidly deployed for treatment. This preliminary characterization eliminates the need for time-consuming isolation and characterization processes during actual patient treatment, while still maintaining patient-specific tumor targeting through selective use of pre-identified TCRs

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent uses T cell receptors (TCRs) as molecular copies or proxies for the actual T cells. Instead of isolating and characterizing entire T cell clones for each patient, the invention uses purified TCR molecules that replicate the antigen-specific recognition functionality. This copying approach maintains patient-specific tumor targeting capability while dramatically reducing the time and complexity required for preparation

Inventive Principle:

Principle #26Copying

2Reliability

If existing ACT technologies are used, then tumor-specific T cell therapy can be provided, but high-avidity T cells are difficult to identify and obtain

Engineering Contradiction:

Improvetumor-specific T cell therapy effectivenessVSAvoididentification of high-avidity T cell clones

Core Design Contradiction:

ReliabilityVSMeasurement precision

Solution Approach 1:

The patent replaces complex mechanical and laboratory-based methods for identifying high-avidity T cell clones with computational and in silico approaches. By using bioinformatics tools to predict TCR-antigen interactions and assess avidity through computational modeling, the invention can precisely identify and select high-avidity TCRs without requiring complex experimental characterization procedures, thus improving measurement precision for avidity assessment

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentUS20250346648A1MAGE a4 t cell receptors

Publication Date: 2025.11.13 REGENERON PHARMACEUTICALS INC

AI summary

The present invention relates to an isolated T cell receptor (TCR) specific for MAGE-A4 and a polypeptide comprising a functional portion of the TCR. Further implicated are a multivalent TCR complex, a nucleic acid encoding a TCR, a cell expressing the TCR and a pharmaceutical composition comprising the TCR. The invention also refers to the TCR for use as a medicament, in particular to the TCR for use in the treatment of cancer.