TCR Constructs Targeting COL6A3 Antigens for Cancer Therapy
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Solution Overview
Problem
Current cancer therapies lack specific targeting mechanisms to effectively target cancer cells, particularly those expressing the COL6A3 antigen, which is associated with various cancers and serves as a potential prognosis marker.
Innovation Solution
Development of novel T cell receptor (TCR) constructs with high specificity and selectivity for the COL6A3 antigen, comprising complementary determining regions (CDR) sequences that enable specific binding to COL6A3 epitopes presented by HLA molecules, facilitating targeted immune responses against cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current cancer therapies are used, then treatment can be provided, but they lack specific targeting mechanisms to effectively target cancer cells expressing COL6A3 antigen
Solution Approach 1:
The patent introduces T cell receptors (TCRs) as intermediary molecules that specifically bind to COL6A3 antigen presented by HLA molecules on cancer cells. These TCRs act as mediators between the immune system and the tumor, enabling specific recognition and targeting of COL6A3-expressing cancer cells while sparing normal cells. The TCRs include variable regions with CDR3 sequences that provide high specificity for the antigen, resolving the contradiction by introducing a targeted mechanism that increases both reliability of cancer targeting and quantity of targeted immune response.
2Reliability
If TCR constructs with high specificity for COL6A3 are developed, then targeted immune response is enhanced, but this requires novel molecular constructs with specific CDR sequences
Solution Approach 1:
The patent applies local quality by focusing specificity enhancement on the CDR3 regions of the TCR variable domains. Rather than redesigning entire TCR molecules, the invention optimizes specific local segments (CDR3 sequences) that directly contact the antigen. This approach achieves high specificity for COL6A3 while managing overall construct complexity by maintaining standard TCR framework structures and only modifying the critical antigen-binding CDR3 regions with sequences of 10-15 amino acids that provide the necessary specificity.
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 TCR constructs induce significant interferon-γ secretion by T cells upon encountering COL6A3-expressing cells, demonstrating high avidity and specificity, potentially leading to effective cancer treatment and prevention by enhancing immune recognition and destruction of cancer cells.
Implementation Method 1
TCR constructs with high specificity and selectivity for the COL6A3 antigen, comprising complementary determining regions (CDR) sequences that enable specific binding to COL6A3 epitopes presented by HLA molecules
Implementation Method 2
The TCR constructs induce significant interferon-γ secretion by T cells upon encountering COL6A3-expressing cells, demonstrating high avidity and specificity, potentially leading to effective cancer treatment and prevention by enhancing immune recognition and destruction of cancer cells
Data Source
AI summary
The present invention pertains to antigen recognizing constructs against COL6A3 antigens. The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for the tumor expressed antigen COL6A3. The TCR of the invention, and COL6A3 antigen binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of COL6A3 expressing cancerous diseases. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention.