In Vitro Epitope Identification Using Dendritic Cells
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Solution Overview
Problem
Biopharmaceuticals often exhibit immunogenicity, leading to potency loss and adverse events due to the presence of T cell epitopes, which trigger immune reactions, and existing methods for identifying these epitopes are inefficient or unreliable.
Innovation Solution
An in vitro method is developed to isolate and sequence immunogenic peptides from human dendritic cells pulsed with pharmaceutical proteins, specifically targeting MHC II molecule-immunogenic peptide complexes to reduce immunogenicity by modifying the corresponding epitopes, thereby creating non-immunogenic biopharmaceuticals.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If in silico prediction algorithms or in vitro screening of overlapping synthetic peptides are used to identify epitopes, then the identification process can be performed, but the methods are inefficient and unreliable
Solution Approach 1:
The patent uses dendritic cells as an intermediary system to naturally process and present peptide epitopes through MHC class II molecules. This biological mediator provides a more reliable and physiologically relevant identification method compared to in silico predictions or synthetic peptide screening, while maintaining practical efficiency through in vitro culture systems.
Solution Approach 2:
The method allows dendritic cells to self-process the pharmaceutical protein and self-present the resulting peptide epitopes through their natural MHC class II molecules. This self-service approach eliminates the need for external prediction algorithms or complex synthetic peptide libraries, improving both reliability and efficiency.
2Object-affected harmful factors
If T cell epitopes are present in biopharmaceuticals, then immunogenicity occurs leading to potency loss and adverse events, but removing or modifying these epitopes may affect therapeutic function
Solution Approach 1:
The patent applies local quality modification by specifically targeting and modifying only the immunogenic epitope regions of the pharmaceutical protein while leaving the rest of the therapeutic molecule intact. This localized approach reduces immunogenicity without compromising the overall therapeutic function and bioactivity of the biopharmaceutical.
Solution Approach 2:
The method involves changing the amino acid sequence parameters of identified epitopes through site-directed mutagenesis. By modifying specific residues within epitopes while maintaining their structural and functional properties, the patent reduces immunogenicity potential while preserving therapeutic potency.
Data Source
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AI summary
The present invention relates to a method for identifying peptides involved in immunogenicity comprising the steps of a) providing cells expressing antigen presenting receptors (APR) in a number providing 0.1 to 5 ug molecules, b) contacting the cells from (a) with a source of immunogenic peptides, c) isolating APR molecule-immunogenic peptide complexes from the cells, d) cluting the associated peptides from the APR molecules, e) identifying the immunogenic peptides, f) verifying the identified immunogenic peptides as cpitopcs.