TL1A Antibodies Targeting Specific Epitopes to Reduce Immunogenicity
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Solution Overview
Problem
Current TL1A-targeting antibodies face issues with immunogenicity, high dosage, and frequent administration, as evidenced by high anti-drug antibody (ADA) and neutralizing antibody (NAb) formation, which complicates their therapeutic efficacy in treating autoimmune and inflammatory diseases.
Innovation Solution
Development of novel TL1A antibodies that bind to specific epitopes, forming smaller immune complexes with TL1A, reducing immunogenicity, and optionally modifying the Fc region for enhanced pH-dependent binding and increased half-life, thereby improving biological activity and pharmacokinetic properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current TL1A-targeting antibodies are used, then therapeutic efficacy is achieved, but immunogenicity increases leading to high anti-drug antibody formation
Solution Approach 1:
The patent applies parameter changes by modifying the antibody structure to bind to a specific epitope (amino acid residues 102-105 in the TL1A signal peptide region) rather than conventional epitopes. This structural parameter change reduces immunogenicity while maintaining therapeutic efficacy, as the antibody forms smaller immune complexes that are less recognized by the immune system.
2Reliability
If current TL1A antibodies are administered, then therapeutic effect is achieved, but dosage frequency must be high
Solution Approach 1:
The patent employs dynamics by engineering the antibody's Fc region to exhibit pH-dependent binding characteristics. The antibody binds TL1A strongly at neutral pH (therapeutic effect) but releases it at acidic pH (in endosomes/lysosomes), enabling targeted degradation. This dynamic behavior extends the antibody's functional half-life and reduces administration frequency.
3Reliability
If current TL1A antibodies form immune complexes, then TL1A is neutralized, but complex size increases immunogenicity
Solution Approach 1:
The patent applies local quality by targeting a specific local region (epitope in the signal peptide sequence at amino acid residues 102-105) of the TL1A protein. This localized binding produces smaller immune complexes compared to conventional antibodies, reducing their recognition by the immune system while maintaining effective TL1A neutralization.
Data Source
AI summary
The present disclosure relates to antibodies that specifically binding to TL1A and uses thereof, in particular to antibodies that specifically bind to TL1A or antigen-binding fragments thereof, nucleic acids encoding the antibodies or antigen-binding fragments thereof, vectors containing the nucleic acids, and host cells containing the nucleic acids or the vectors. Pharmaceutical compositions comprising the antibodies as well as methods of treatment using the antibodies are also provided.