introduction: haemophilia a is the most common inherited x-linked recessive bleeding disorder. the severity of the resultant bleeding diathesis depends on the fviii levels associated with the mutation. analysis of carrier state can be made indirectly by dna linkage analysis or directly by identifying the mutation that leads to the disease. the aim of this study was to identification of the caus...

Purpose: Interleukin-12 (IL12) is a potent proinflammatory cytokine with antitumor activity. Its heterodimeric nature makes it compatible with a large variety of different immunocytokine formats. Here we report the design, production, and characterization of a novel immunocytokine, based on the fusion of the F8 antibody (specific to the alternatively spliced EDA domain of fibronectin, a marker ...

Cytokines often display substantial toxicities at low concentrations, preventing their escalation for therapeutic treatment of cancer. Fusion proteins comprising cytokines and recombinant antibodies may improve the anticancer activity of proinflammatory cytokines. Murine IFNg was appended in the diabody format at the C-terminus of the F8 antibody, generating the F8–IFNg fusion protein. The F8 a...

PURPOSE Interleukin-12 (IL12) is a potent proinflammatory cytokine with antitumor activity. Its heterodimeric nature makes it compatible with a large variety of different immunocytokine formats. Here we report the design, production, and characterization of a novel immunocytokine, based on the fusion of the F8 antibody (specific to the alternatively spliced EDA domain of fibronectin, a marker o...

Cytokines often display substantial toxicities at low concentrations, preventing their escalation for therapeutic treatment of cancer. Fusion proteins comprising cytokines and recombinant antibodies may improve the anticancer activity of proinflammatory cytokines. Murine IFNγ was appended in the diabody format at the C-terminus of the F8 antibody, generating the F8-IFNγ fusion protein. The F8 a...

INTRODUCTION Etanercept is a fusion protein consisting of the soluble portion of the p75-tumor necrosis factor receptor (TNFR) and the Fc fragment of human IgG1, which is often used for the treatment of patients with rheumatoid arthritis. F8-IL10 is a human immunocytokine based on the F8 antibody and interleukin-10, which is currently being investigated in rheumatoid arthritis with promising cl...

Hemophilia, a common congenital coagulation disorder, is classified as hemophilia A (HA) and hemophilia B (HB), which result from a deficiency or dysfunction of coagulation factor VIII (FVIII) and factor IX (FIX), respectively. HA is known to be caused by heterogeneous mutations of the FVIII gene (F8), such as inversions, substitutions, deletions, insertions, etc. F8 (NM_000132.3) is located on...

There is an increasing biotechnological interest in 'arming' therapeutic antibodies with bioactive payloads. Many antibody-cytokine fusion proteins (immunocytokines) have been described and some of these biopharmaceuticals have progressed to clinical studies. Here, we describe for the first time the expression and in vivo characterization of immunocytokines based on murine IL1β and IL6. These p...

UNLABELLED ESSENTIALS: Anti-factor VIII (FVIII) inhibitory antibody formation is a severe complication in hemophilia A therapy. We genetically engineered and characterized a mouse model with complete deletion of the F8 coding region. F8(TKO) mice exhibit severe hemophilia, express no detectable F8 mRNA, and produce FVIII inhibitors. The defined background and lack of FVIII in F8(TKO) mice will ...

Hemophilia A (HA) is caused by partial or total deficiency of F8 protein activity. In a small group, about 1.8% of patients with HA, no mutation is found in the F8 gene. Among this group, we report here on one patient with severe HA in whom no mRNA of the F8 gene was detected. Using 2 common polymorphisms in F8 exon 14, we were able to show that the same allele shared by the patient, his mother...