Castle Creek Biosciences’ proprietary autologous fibroblast technology is the foundation of our ex vivo approach for developing personalized, targeted and redosable cell-based, gene therapy product candidates for monogenic, chronic disorders, initially targeting skin and connective tissue.
Fibroblasts, the most common cells in skin and connective tissue, are responsible for synthesizing extracellular matrix proteins, including collagen, which provide structure and support to the skin. In our ex vivo approach, we leverage the clinical benefits of fibroblasts, which are readily isolated from the skin and expanded in culture and have unique qualifications for localized delivery to gene targets in the skin and connective tissue.
We are using our proprietary ex vivo platform, Lenti-VEX, to develop and evaluate D-Fi, also known as FCX-007, (dabocemagene autoficel), an autologous gene therapy candidate for the treatment of dystrophic epidermolysis bullosa (DEB)—a progressive, devastatingly painful and debilitating, rare genetic skin disorder. DEB is caused by a mutation in the COL7A1 gene, leading to a deficiency of normal type VII collagen (COL7) protein, impairing the connection between the epidermis and the dermis.
D-Fi is comprised of a patient’s own dermal fibroblasts that are genetically modified with a self-inactivating (SIN) lentiviral vector (LV) containing the COL7A1 gene to express COL7. D-Fi is locally administered by intradermal injection into the superficial papillary dermis of chronic wounds where the COL7 protein can support the formation of anchoring fibrils in the skin.
Castle Creek Biosciences’ autologous fibroblast technology uses our patented manufacturing process, which involves collecting small skin biopsies from patients, isolating cells and expanding them in culture, transducing the fibroblast cells ex vivo with an integrative SIN-LV to express a protein of interest, followed by continued expansion of the gene-modified cells in culture.1,2 The cells are then locally administered intradermally to sites of active wounds with the goal of expressing the target protein in the desired region in order to restore skin integrity. As part of this process, a personalized cell bank of genetically modified autologous fibroblasts is created that can be stored cryogenically, serving as a repository for a patient’s long term therapeutic needs.
1 M. P. Marinkovich, MD, N. Ehsani-Chimeh, MD, N. Nguyen, S. Moncrief, PhD, V. K. Dailey, M. Chakiath, A. Elayadi, PhD, S. Krishnan, MS, and J. Maslowski, MS. Pre-Clinical Development of a Genetically-Modified Human Dermal Fibroblast (FCX-007) for the Treatment of Recessive Dystrophic Epidermolysis Bullosa. Presented at the American Society of Human Genetics Annual Meeting, Baltimore, Maryland, October 8, 2015.
2 V.K. Dailey, M. Chakiath, A. Elayadi, PhD, S. Krishnan, MS, J. Maslowski, MS, M. P. Marinkovich, MD. Development of a Genetically-Modified Human Dermal Fibroblast for the Treatment of Recessive Dystrophic Epidermolysis Bullosa. Presented at the European Society of Human Genetics, Glasgow, Scotland, United Kingdom, June 8, 2015.
Castle Creek Biosciences’ product candidates are investigational. None of our investigational gene therapies have received marketing approval by the U.S. Food and Drug Administration nor any other regulatory agency
