Abstract Number: OC 59.2
Meeting: ISTH 2021 Congress
Background: Factor VII Deficiency is an autosomal recessive rare bleeding disorder. Current therapy is primarily on demand due in part to short half-life of the factor; additionally, there is only one ongoing clinical trial for this disease, and none investigating any novel modalities.
Aims: We aim to provide long-term, sustained human FVII zymogen (hFVII) production in vivo with an innovative approach using cell therapy with shielded, genetically modified human allogeneic cells.
Methods: We already reported on the development of SIG-009, a novel cell-based product for FVII Deficiency (Carmona EAHAD 2020). First, we genetically modified a human cell line using a non-viral vector. Next, we encapsulated the hFVII-expressing cells in two-compartment, 1.5 mm spheres: the inner compartment contains an alginate matrix optimized to maximize protein production in vivo and the acellular outer layer contains a proprietary mixture of small-molecule-modified and unmodified alginates, which minimizes the pericapsular fibrotic overgrowth (PFO) and cell contact with the host’s immune cells. The resulting SIG-009 spheres are placed in the intraperitoneal space in mice. The spheres are sufficiently porous to allow nutrients and secreted proteins to freely diffuse.
Results: hFVII produced by SIG-009 has high bioavailability from the IP space and it is produced in a dose-dependent manner in vivo. One-month study in NSG mice showed sustained hFVII production and plasma levels in a potentially therapeutic range. Give that mouse model for this disease is not widely available, we conducted efficacy experiments in FVII deficient human plasma. We demonstrated that hFVII produced by SIG-009 is sufficient to activate factor X to factor Xa in vitro. This finding confirmed that the zymogen produced by SIG-009 is successfully converted into the active form of enzyme when needed.
Conclusions: SIG-009 has the potential to provide sustained production of human FVII zymogen and to address a high unmet need in this patient population.
To cite this abstract in AMA style:Kelley E, Patel J, Jansen L, Sparages C, Barrett K, Smith D, Makino E, Donovan M. SIG-009: Novel Encapsulated Non-viral Cell-based Therapy for FVII Deficiency [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/sig-009-novel-encapsulated-non-viral-cell-based-therapy-for-fvii-deficiency/. Accessed November 29, 2023.
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