Affinity ranking and characterization of bispecific albumin-binding domains with high affinity for ErB3
Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Small bispecific affinity proteins represent interesting alternatives to antibodies in the field of biotherapeutics. They have the same potential as antibodies to be engineered into target specific proteins, despite their small size. The small size may also lead to increased tumor access as well as elevated tissue penetration abilities. However, the circulation time in vivo is generally short for small molecules, which affects their therapeutic potential. By utillizing protein domains with inherent affinity for albumin, we have addressed this problem and possibly prolonged the half-life without increasing the size of the proteins. These albumin-binding domains (ABDs) have been engineered into high-affinity ErbB3 binders and with this study we hav shown that selection, together with characterization can identify ABD molecules with affinity for ErbB3 in the subnanomolar range. The smallest, bispecific ErbB3-targeting proteins so far, have been identified by this study and represent promising alternatives in cancer therapy, with their potential ability to inhibit ErbB3-signaling.
Place, publisher, year, edition, pages
ABD, affinity, selection
Engineering and Technology
IdentifiersURN: urn:nbn:se:kth:diva-150556OAI: oai:DiVA.org:kth-150556DiVA: diva2:744721
Åstrand, MikaelNilvebrant, Johan