MAGEB2 Antigen Binding Proteins Targeting Intracellular Cancer Antigens
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Solution Overview
Problem
Current cancer therapies lack specificity and efficacy in targeting intracellular cancer-testis antigens like MAGEB2, which are highly specific to cancer cells but difficult to access with existing treatments.
Innovation Solution
Development of novel antigen binding proteins specifically designed to bind to the MAGEB2 antigenic peptide in complex with MHC proteins, featuring high stability, affinity, functional avidity, and specificity, and are capable of targeting intracellular proteins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If TCR based immunotherapy is used to target intracellular proteins, then the number and diversity of targets increases, but the complexity of the therapeutic approach increases
Solution Approach 1:
The patent segments the TCR complex into separate variable domains (Vα and Vβ) that can be independently engineered and combined with different constant domains to create modular therapeutic constructs. This allows systematic targeting of multiple intracellular antigens while maintaining manageable complexity through standardized domain architectures.
Solution Approach 2:
The patent creates universal TCR constructs with standardized constant domains (such as IgG Fc regions) that can be combined with various variable domains targeting different MAGEB2 epitopes. This multi-functional platform enables a single therapeutic framework to address multiple cancer targets through domain swapping and combinatorial assembly.
2Reliability
If antigen binding proteins are designed with high specificity to MAGEB2, then therapeutic efficacy improves, but the risk of off-target effects and immune response increases
Solution Approach 1:
The patent applies local quality by engineering specific CDR regions within the TCR variable domains to achieve precise epitope recognition. The CDR3 regions are particularly optimized for high-affinity binding to MAGEB2 peptide-MHC complexes, while framework regions maintain structural stability and reduce immunogenicity. This localized optimization allows high specificity without compromising overall safety.
Solution Approach 2:
The patent uses soluble antigen binding proteins as intermediaries that can modulate the immune response. These engineered proteins can act as blocking agents or enhancing molecules that regulate T cell activation, providing a safety mechanism to control off-target effects while maintaining therapeutic efficacy against MAGEB2-expressing tumors.
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
These antigen binding proteins demonstrate high cytotoxicity against tumor cells, improved safety profiles compared to prior art, and enhanced therapeutic efficacy in treating MAGEB2-expressing cancers.
Implementation Method 1
an antigen binding protein specifically binding to a MAGEB2 antigenic peptide that is in a complex with a major histocompatibility complex (MHC) protein
Data Source
AI summary
The present invention relates to antigen binding proteins that specifically bind to a tumor expressed melanoma-associated antigen (MAGE) B2 antigenic peptide in a complex with MHC. The antigen binding proteins are provided for use in the treatment of MAGEB2-expressing cancers. Further provided are nucleic acids encoding the antigen binding proteins, vectors comprising the nucleic acids, recombinant cells expressing the antigen binding proteins and pharmaceutical compositions comprising the antigen binding proteins.