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A bispecific antibody approach for the potential prophylactic treatment of inherited bleeding disorders.
Gandhi, Prafull S; Zivkovic, Minka; Østergaard, Henrik; Bonde, Amalie C; Elm, Torben; Løvgreen, Monika N; Schluckebier, Gerd; Johansson, Eva; Olsen, Ole H; Olsen, Eva H N; de Bus, Ian-Arris; Bloem, Karien; Alskär, Oskar; Rea, Catherine J; Bjørn, Søren E; Schutgens, Roger E; Sørensen, Benny; Urbanus, Rolf T; Faber, Johan H.
Afiliación
  • 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.
Nat Cardiovasc Res ; 3(2): 166-185, 2024 02.
Article en En | MEDLINE | ID: mdl-39196196
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anticuerpos Biespecíficos Límite: Animals / Female / Humans / Male Idioma: En Revista: Nat Cardiovasc Res Año: 2024 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anticuerpos Biespecíficos Límite: Animals / Female / Humans / Male Idioma: En Revista: Nat Cardiovasc Res Año: 2024 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido