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

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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.

I: Nature Cardiovascular Research, Bind 3, Nr. 2, 2024, s. 166-185.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Gandhi, PS, Zivkovic, M, Østergaard, H, Bonde, AC, Elm, T, Løvgreen, MN, Schluckebier, G, Johansson, E, Olsen, OH, Olsen, EHN, de Bus, IA, Bloem, K, Alskär, O, Rea, CJ, Bjørn, SE, Schutgens, RE, Sørensen, B, Urbanus, RT & Faber, JH 2024, 'A bispecific antibody approach for the potential prophylactic treatment of inherited bleeding disorders', Nature Cardiovascular Research, bind 3, nr. 2, s. 166-185. https://doi.org/10.1038/s44161-023-00418-4

APA

Gandhi, P. S., Zivkovic, M., Østergaard, H., Bonde, A. C., Elm, T., Løvgreen, M. N., Schluckebier, G., Johansson, E., Olsen, O. H., Olsen, E. H. N., de Bus, I. A., Bloem, K., Alskär, O., Rea, C. J., Bjørn, S. E., Schutgens, R. E., Sørensen, B., Urbanus, R. T., & Faber, J. H. (2024). A bispecific antibody approach for the potential prophylactic treatment of inherited bleeding disorders. Nature Cardiovascular Research, 3(2), 166-185. https://doi.org/10.1038/s44161-023-00418-4

Vancouver

Gandhi PS, Zivkovic M, Østergaard H, Bonde AC, Elm T, Løvgreen MN o.a. A bispecific antibody approach for the potential prophylactic treatment of inherited bleeding disorders. Nature Cardiovascular Research. 2024;3(2):166-185. https://doi.org/10.1038/s44161-023-00418-4

Author

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. / A bispecific antibody approach for the potential prophylactic treatment of inherited bleeding disorders. I: Nature Cardiovascular Research. 2024 ; Bind 3, Nr. 2. s. 166-185.

Bibtex

@article{2aca6ac3d2604cd397b186d84d664a0f,
title = "A bispecific antibody approach for the potential prophylactic treatment of inherited bleeding disorders",
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.",
author = "Gandhi, {Prafull S.} and Minka Zivkovic and Henrik {\O}stergaard and Bonde, {Amalie C.} and Torben Elm and L{\o}vgreen, {Monika N.} and Gerd Schluckebier and Eva Johansson and Olsen, {Ole H.} and Olsen, {Eva H.N.} and {de Bus}, {Ian Arris} and Karien Bloem and Oskar Alsk{\"a}r and Rea, {Catherine J.} and Bj{\o}rn, {S{\o}ren E.} and Schutgens, {Roger E.} and Benny S{\o}rensen and Urbanus, {Rolf T.} and Faber, {Johan H.}",
note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",
year = "2024",
doi = "10.1038/s44161-023-00418-4",
language = "English",
volume = "3",
pages = "166--185",
journal = "Nature Cardiovascular Research",
issn = "2731-0590",
publisher = "Springer Nature [academic journals on nature.com]",
number = "2",

}

RIS

TY - JOUR

T1 - A bispecific antibody approach for the potential prophylactic treatment of inherited bleeding disorders

AU - Gandhi, Prafull S.

AU - Zivkovic, Minka

AU - Østergaard, Henrik

AU - Bonde, Amalie C.

AU - Elm, Torben

AU - Løvgreen, Monika N.

AU - Schluckebier, Gerd

AU - Johansson, Eva

AU - Olsen, Ole H.

AU - Olsen, Eva H.N.

AU - de Bus, Ian Arris

AU - Bloem, Karien

AU - Alskär, Oskar

AU - Rea, Catherine J.

AU - Bjørn, Søren E.

AU - Schutgens, Roger E.

AU - Sørensen, Benny

AU - Urbanus, Rolf T.

AU - Faber, Johan H.

N1 - Publisher Copyright: © The Author(s) 2024.

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

U2 - 10.1038/s44161-023-00418-4

DO - 10.1038/s44161-023-00418-4

M3 - Journal article

AN - SCOPUS:85184429737

VL - 3

SP - 166

EP - 185

JO - Nature Cardiovascular Research

JF - Nature Cardiovascular Research

SN - 2731-0590

IS - 2

ER -

ID: 383397919