Cellular mutations generate neoepitopes that play a key role in the immunotherapy of cancer. However, most of the candidate neoepitopes obtained by high-throughput sequencing are not immunogenic when tested in vivo or in vitro, and these large number of potential candidate epitopes require further screening and identification. Creative BioMart offers MHC neoepitope discovery services, including the selection, characterization and monitoring studies of immunogenic neoepitopes for the design of therapeutic cancer vaccines and T-cell therapies, as well as an ever-expanding neoepitope dataset for client program development.

Epitope Discovery and Vaccine Design

There is great potential for immune-mediated cancer vaccine therapeutic strategies in which these immunogens activate cytotoxic T cells to selectively target and eradicate cancer cells, which is achieved through T cell recognition of tumor antigen epitopes presented by tumor cells on MHC molecules. Thus, the discovery of MHC neo-antigenic epitopes is essential for the design of therapeutic cancer vaccines and immunotherapies.

Designing synthetic vaccines based on short peptides representing immunogenic epitopes allows us to explore antigen processing, binding to MHC class I and II, and TCR recognition through various epitope analysis and prediction tools. The development of epitope-based vaccines combining immunoinformatics and experimental biology approaches using empirical and computer tools can improve the efficacy of existing vaccines and they are more advantageous compared to conventional vaccines.

Our Solutions

Our study provides a feasible and efficient way to implement a solution for selecting specific T cell neo-epitopes from a set of candidate epitopes, analyzing both mutated neo-epitopes, as well as insertions, deletions, translocations, fusions, etc. The goal is to discover and select more immunogenic epitopes for the client's therapeutic development program.

Fig.1 Our solutions for the discovery of MHC neoepitopes

• We can collate mutated and modified MHC epitopes from cancer antigens from the literature, databases, to generate a dataset of epitopes covering cancer mutations and their corresponding non-mutated counterparts in antigenic peptides that can be used for project-specific screening and applications.
• Our services include measuring the binding affinity of antigenic peptides for purified MHC using purification of MHC-like molecules and quantitative competitive inhibition assays, as well as comparing the relative ability of each peptide to bind each specific allele to determine its stability.
• Neoepitopes are evaluated for similarity to corresponding non-mutant epitopes as well as for immunogenicity and validation of specificity.

Research Tools

Epitope discovery is increasingly dependent on bioinformatics analysis tools and databases for accessing data. We provide epitope discovery first solutions to help biomedical researchers develop new vaccines, diagnostics and therapeutics, with analysis resources available to all researchers and tools for analysis and prediction of various epitopes.

• Sequence-Based epitope prediction
• Structure-based epitope prediction
• MHC binding experiments
• MHC binding prediction tools
• T-cell immunogenicity prediction tools
• Machine learning and predictive evaluation
• Analysis tools

Creative BioMart provides a comprehensive strategy for discovery and prediction of new MHC-like epitopes and an epitope validation approach using T-cell stimulation for the design of targeted vaccines and cellular therapies to improve the efficiency of vaccine antigen epitope selection.

To learn about the many valuable and rich bioinformatics resources for MHC-related epitopes, please contact us for support with your project.

Reference

• Zeynep K Y, et al. "Predicting T cell recognition of MHC class I restricted neoepitopes." Oncoimmunology (2018), 7,11.