Increasing the potency of neutralizing single-domain antibodies by functionalization with a CD11b/CD18 binding domain.

摘要: Recombinant single domain antibodies (nanobodies) constitute an attractive alternative for the production of neutralizing therapeutic agents. Their small size warrants rapid bioavailability and fast penetration to sites toxin uptake, but also renal clearance, which negatively affects their performance. In this work, we present a new strategy drastically improve potency based on fusion second nanobody specific complement receptor CD11b/CD18 (Mac-1). These bispecific retain (˜30 kDa), acquire effector functions that promote elimination toxin-immunocomplexes. The principle was demonstrated in mouse model lethal toxicity with tetanus toxin. Three anti-tetanus nanobodies were selected characterized terms overlapping epitopes inhibition binding neuron gangliosides. Bispecific constructs most promising monodomain built using anti Mac-1, CD4...