Engineering of bispecific affinity proteins with nanomolar affinity for both ErbB2 and albumin
(English)Manuscript (preprint) (Other academic)
The epidermal growth factor receptor 2, ErbB2, is a well-validated target for cancer therapy. Recent studies suggest that the over-expression of this receptor in various cancers might also be exploited for antibody-based payload delivery, e.g. antibody drug conjugates. In such strategies, the full-length antibody format is probably not required for therapeutic effect and smaller tumor-antigen specific affinity proteins might be an alternative. However, small proteins and peptides generally suffer from fast excretion through the kidneys, requiring frequent administration in order to maintain a therapeutic concentration. In an attempt aimed at combining ErbB2- targeting with antibody-like pharmacokinetic properties, we have engineered bispecific ErbB2-binding affinity proteins that are based on a small albumin-binding domain. Phage display technology was used for identification of a lead candidate as well as for affinity maturation using second-generation libraries. Affinity matured binders were shown to bind human ErbB2 with high affinity while still retaining the natural interaction with human serum albumin. Hence, two important properties that may be utilized for tumor targeting and in vivo half-life extension were combined in one molecule.
IdentifiersURN: urn:nbn:se:kth:diva-105516OAI: oai:DiVA.org:kth-105516DiVA: diva2:571302
QS 20122012-11-222012-11-222012-11-22Bibliographically approved