Adding Effector Functions to Single-Domain Antibodies by Functionalization with a CD lib/CD 18 Binding Domain

摘要

Highly potent in vitro neutralizing nanobodies are easily obtained from phage display libraries prepared from peripheral lymphocytes obtained from camelids immunized with the toxin. Their small size (approx15 kDa) warrants a rapid bioavailability and fast penetration to sites of toxin uptake, but also their rapid renal clearance which negatively affects their in vivo performance. Here we present a novel strategy to dramatically increase the neutralizing potency of single domain antibodies based on their fusion to a second nanobody specific for the complement receptor CD11b/CD18, highly expressed in neutrophils, monocytes and macrophages.