SciCross can support de-immunization efforts of biopharmaceutical by in silico assessment, focused on the removal of T-cell epitopes. This can be achieved by suggesting amino acid substitution of the original 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).
Schubert B, Schärfe C, Dönnes P, Hopf T, Marks D, Kohlbacher O. Population-specific design of de-immunized protein biotherapeutics. PLoS Comput Biol. 2018;14(3):e1005983. (pubmed).