The monoclonal antibody KM33 acts as a high-affinity ligand that can inhibit the function of blood coagulation factor VIII (FVIII). In vitro, KM33 inhibits FVIII activity and interactions with its physiological ligands, von Willebrand factor, phospholipids and catabolic receptors.
Figure 1 fVIII functional assays in the presence of group A, AB, and B anti-C1 mAbs.
(A) Inhibition of fVIII procoagulant activity by type 2 group A mAb I84 (●), type 1 group AB mAb KM33 (▪), and type 1 group B mAb B136 (△) by Bethesda assay. (B) Inhibition of fVIII binding to PCPS and (C) fVIII binding to VWF in the presence of anti-C1 mAbs group A B153 (●), group AB KM33 (▪), and group B B136 (△) determined by competitive ELISAs.
Batsuli, G., Deng, W., Healey, J. F., Parker, E. T., Baldwin, W. H., Cox, C., ... & Lollar, P. (2016). High-affinity, noninhibitory pathogenic C1 domain antibodies are present in patients with hemophilia A and inhibitors. Blood, 128(16), 2055-2067.
Figure 2 Inhibition of uptake of fVIII by dendritic cells by anti-C1 mAbs.
Flow cytometric histograms of 10 nM DyLight 650-conjugated recombinant full-length fVIII uptake by human MDDCs in the absence and presence of 80 nM group AB KM33. Representative histograms of untreated (gray) and treated (white) MDDCs displaying the percentage of internalized fVIII in the absence or presence of the anti-C1 mAbs tested are shown. Percentages of fVIII uptake shown in the insets were estimated by the integrated fluorescence beyond the control histogram.
Batsuli, G., Deng, W., Healey, J. F., Parker, E. T., Baldwin, W. H., Cox, C., ... & Lollar, P. (2016). High-affinity, noninhibitory pathogenic C1 domain antibodies are present in patients with hemophilia A and inhibitors. Blood, 128(16), 2055-2067.
Figure 3 Inhibition of uptake of fVIII by dendritic cells by anti-C1 mAbs.
Median fluorescence intensities of human MDDCs incubated with increasing concentrations of DyLight 650-conjugated fVIII alone (control) and in the presence of mAbs 2A9, F156, I84, KM33, and B136.
Batsuli, G., Deng, W., Healey, J. F., Parker, E. T., Baldwin, W. H., Cox, C., ... & Lollar, P. (2016). High-affinity, noninhibitory pathogenic C1 domain antibodies are present in patients with hemophilia A and inhibitors. Blood, 128(16), 2055-2067.
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PFBL-051 | Mouse Anti-F8 Recombinant Antibody (clone 3E6); Fab Fragment | ELISA, WB, FuncS | Mouse Fab |
PFBL-052 | Mouse Anti-F8 Recombinant Antibody (clone G99); Fab Fragment | ELISA, WB, FuncS | Mouse Fab |
HPAB-0793-FY-S(P) | Mouse Anti-F8 Recombinant Antibody (clone 4F143); Fab Fragment | Activ | Mouse Fab |
HPAB-0794-FY-S(P) | Mouse Anti-F8 Recombinant Antibody (clone 4F50); Fab Fragment | Activ | Mouse Fab |
HPAB-1242WJ-F(E) | Human Anti-F8 Recombinant Antibody (clone YK3.3.40); Fab Fragment | ELISA | Human Fab |
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Gly-014LC | Recombinant Anti-Human F8 Antibody (Fab glycosylation) | ELISA | Human antibody |
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Gly-015LC | Recombinant Anti-Human F8 Antibody (Non-glycosylated) | ELISA | Human antibody |
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MOB-0376MZ | Recombinant Mouse Anti-Human Factor VIII Antibody (clone BIWIV-5026) | WB, ELISA | Mouse antibody |
HPAB-1977-FY | Human Anti-F8 Recombinant Antibody (clone 92-137) | Inhib | Human IgG |
HPAB-1978-FY | Human Anti-F8 Recombinant Antibody (clone 92-102) | Inhib | Human IgG |
HPAB-1979-FY | Human Anti-F8 Recombinant Antibody (clone WR8) | IP | Human IgG4 |
HPAB-1980-FY | Human Anti-F8 Recombinant Antibody (clone WR11) | IP | Human IgG4 |
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PABX-058 | Recombinant Human Anti-F8 Antibody (BO2C11) | WB, ELISA, FuncS, Inhib, PK, IP, SPR | IgG |
PABX-058-S (P) | Recombinant Human Anti-F8 Antibody scFv Fragment (BO2C11) | WB, ELISA, FuncS | scFv |
PABX-058-F (E) | Recombinant Human Anti-F8 Antibody Fab Fragment (BO2C11) | WB, ELISA, FuncS | Fab |
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NEUT-765CQ | Mouse Anti-F8 Recombinant Antibody (clone CBL215) | ELISA, WB, Neut | Mouse IgG2a |
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MOR-1229 | Hi-Affi™ Rabbit Anti-F8 Recombinant Antibody (clone DS1229AB) | ELISA | Rabbit IgG |
MOR-4166 | Hi-Affi™ Rabbit Anti-F8 Recombinant Antibody (clone SI243DS) | ELISA | Rabbit IgG |
MOR-4167 | Hi-Affi™ Rabbit Anti-F8 Recombinant Antibody (clone SI244DS) | ELISA | Rabbit IgG |
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EPAF-0611LC | Human Anti-F8 Recombinant Antibody (clone BO2C11) | ELISA | Human IgG4 |
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FAMAB-0037JF-S(P) | Human Anti-F8 Recombinant Antibody (clone MH8); scFv Fragment | IP, ELISA, FuncS | Human scFv |
FAMAB-0038JF-S(P) | Human Anti-F8 Recombinant Antibody (clone DH10); scFv Fragment | IP, ELISA, FuncS | Human scFv |
FAMAB-0039JF-S(P) | Human Anti-F8 Recombinant Antibody (clone JM4); scFv Fragment | IP, ELISA, FuncS | Human scFv |
FAMAB-0200JF-S(P) | Human Anti-F8 Recombinant Antibody (clone KM41); scFv Fragment | WB, ELISA, FuncS | Human scFv |
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