Removal of potential T-cell epitopes can reduce the immunogenicity risk of biopharmaceuticals. This can be done by a combination of in silico assessment and protein engineering. SciCross algorithms can identify amino acid substitutions in the original protein sequence that destroy/reduce peptide binding to HLA molecules. Suggested variants can be assessed by different in vitro methods before continued development. An example of how a single amino acid change can reduce the overall immunogenicity risk can be seen below. In general the potential effect of e.g. protein stability should also be considered. With collaborators we have adressed this type of optimisation (reduce immunogenicity while keeping stability) for Factor VIII (Schubert et al., 2018).
