High Avidity Antigen Constructs for MAGE-A1 Targeting
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Solution Overview
Problem
Current immunotherapy approaches for cancer, particularly adoptive T-cell therapy, face challenges in achieving high specificity and avidity against tumor-associated antigens like MAGE-A1, limiting their effectiveness in targeting cancer cells while sparing normal tissues.
Innovation Solution
Development of novel high avidity antigen recognizing constructs, such as antibodies or T cell receptors, specifically designed to bind with high affinity to the melanoma-associated antigen MAGE-A1, along with methods for their production and application in immune cancer therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional T cell therapy is used to target tumor-associated antigens, then the treatment can be administered to patients, but the specificity and avidity against tumor cells are insufficient, limiting effectiveness
Solution Approach 1:
The patent modifies the T cell receptor parameters by engineering chimeric TCRs with altered amino acid sequences that enhance binding affinity and avidity to MAGE-A1 antigen, directly resolving the contradiction between reliability and productivity in cancer treatment
2Measurement precision
If high avidity antigen recognizing constructs are developed to improve targeting precision, then specificity against MAGE-A1 increases, but the complexity of construct design and production increases
Solution Approach 1:
The patent segments the T cell receptor into distinct domains (variable and constant regions) and recombines them from different sources to create chimeric TCRs, enabling precise targeting of MAGE-A1 while managing design complexity through modular construction
Solution Approach 2:
The patent uses engineered T cell receptors as intermediaries that bridge the gap between the immune system and tumor cells expressing MAGE-A1, providing specific recognition while simplifying the overall therapeutic approach
Data Source
AI summary
The present invention pertains to novel high avidity antigen recognizing constructs, such as antibodies or T cell receptors, which specifically bind to the melanoma associated antigen (MAGE) A1. The constructs of the invention are particularly useful for the diagnosis, prevention or therapy of tumorous diseases which are characterized by the specific expression of the MAGE-A1 antigen. Furthermore provided are nucleic acids, vectors and host cells—such as CD4 or CD8 positive T cells—which encode, comprise or present the antigen recognizing constructs of the invention. The invention thus provides new approaches for immune therapy, specifically adoptive T cell therapy, for treating cancer.