A bispecific antibody approach for the potential prophylactic treatment of inherited bleeding disorders.

Autor: Gandhi PS; Hemab Therapeutics, Copenhagen, Denmark. prafull@hemab.com., Zivkovic M; Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands., Østergaard H; Hemab Therapeutics, Copenhagen, Denmark., Bonde AC; Hemab Therapeutics, Copenhagen, Denmark., Elm T; Novo Nordisk A/S, Måløv, Denmark., Løvgreen MN; Novo Nordisk A/S, Måløv, Denmark., Schluckebier G; Novo Nordisk A/S, Måløv, Denmark., Johansson E; Novo Nordisk A/S, Måløv, Denmark., Olsen OH; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark., Olsen EHN; EO Assay Consult, Ballerup, Denmark., de Bus IA; Sanquin Diagnostic Services, Amsterdam, Netherlands., Bloem K; Sanquin Diagnostic Services, Amsterdam, Netherlands., Alskär O; qPharmetra, Stockholm, Sweden., Rea CJ; Hemab Therapeutics, Copenhagen, Denmark., Bjørn SE; Cymab Therapeutics, Copenhagen, Denmark., Schutgens RE; Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands., Sørensen B; Hemab Therapeutics, Copenhagen, Denmark., Urbanus RT; Center for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands. r.t.urbanus@umcutrecht.nl., Faber JH; Hemab Therapeutics, Copenhagen, Denmark.
Jazyk: angličtina
Zdroj: Nature cardiovascular research [Nat Cardiovasc Res] 2024 Feb; Vol. 3 (2), pp. 166-185. Date of Electronic Publication: 2024 Feb 08.
DOI: 10.1038/s44161-023-00418-4
Abstrakt: Inherited bleeding disorders such as Glanzmann thrombasthenia (GT) lack prophylactic treatment options. As a result, serious bleeding episodes are treated acutely with blood product transfusions or frequent, repeated intravenous administration of recombinant activated coagulation factor VII (rFVIIa). Here we describe HMB-001, a bispecific antibody designed to bind and accumulate endogenous FVIIa and deliver it to sites of vascular injury by targeting it to the TREM (triggering receptor expressed on myeloid cells)-like transcript-1 (TLT-1) receptor that is selectively expressed on activated platelets. In healthy nonhuman primates, HMB-001 prolonged the half-life of endogenous FVIIa, resulting in its accumulation. Mouse bleeding studies confirmed antibody-mediated potentiation of FVIIa hemostatic activity by TLT-1 targeting. In ex vivo models of GT, HMB-001 localized FVIIa on activated platelets and potentiated fibrin-dependent platelet aggregation. Taken together, these results indicate that HMB-001 has the potential to offer subcutaneous prophylactic treatment to prevent bleeds in people with GT and other inherited bleeding disorders, with a low-frequency dosing regimen.
(© 2024. The Author(s).)
Databáze: MEDLINE
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