PreDeFT Analysis

Pre-Deimmunization of a Functional Therapeutic Report

EpiVax’s PreDeFT Report is a comprehensive description of a protein therapeutic candidate’s immunogenic potential including expert considerations for indication, mechanism of action, and intended patient population. The PreDeFT analysis relies on the EpiMatrix platform to parse a protein candidate into all possible amino acid-based HLA ligands. Each is then assessed for its ability to bind to a set of nine common class II HLA allele supertypes and, if applicable, six common class I HLA allele supertypes.

Every HLA allele supertype used in the EpiMatrix platform represents a large family of closely related alleles that share amino acid binding affinities, and thus the analysis evaluates potential T cell dependent immune responses for over 95% of the global human population.[1]

 

Peptides that have a high likelihood of binding and being presented by HLA molecules on the surface of antigen-presenting cells (APCs), such as dendritic cells and macrophages, are considered T cell epitopes, a vital component of the peptide/HLA complex which is critical for initiating a T cell dependent immune response.

Graphical scale of immunogenicity

If analyzing an antibody or antibody fragments, the PreDeFT analysis will also identify validated regulatory T cell epitopes that may be present in your sequence. Tregitopes can activate natural regulatory T cells and dampen an unwanted immune responses. The detailed findings from the EpiMatrix analysis are then summarized, producing an overall assessment of immunogenic potential and a method for ranking your protein therapeutic candidate(s) against other known immunogenic and non-immunogenic protein sequences.

In addition to the overall assessment of immunogenic potential, the PreDeFT analysis includes the identification of specific regions that have the potential to trigger an immune response. These regions, or “clusters”, identified during the analysis are further evaluated for human cross-conservation using JanusMatrix, an indicator of regulatory or tolerogenic potential. Regions of high epitope density are then individually assessed for potential risk, identifying for you specific sites as targets for deimmunization or redesign.

Our global and regional assessments are well-correlated with observed immunogenicity and can effectively direct R&D strategies and support regulatory filings.

We understand that our clients may be at various stages of development and the EpiVax team will work with you to understand your needs and customize the PreDeFT Report to fit any project or development stage.

Looking to screen a large set of candidates for relative immunogenic potential? Check out our ISPRI-HT (high throughput) Analysis or gain access to our ISPRI toolkit.

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[1] Southwood S, Sidney J, Kondo A, del Guercio MF, Appella E, Hoffman S, et al. Several common HLA-DR types share largely overlapping peptide binding repertoires. J Immunol. 1998 Apr 1; 160(7):3363–73. PMID: 9531296