Autologous Fibroblast Technology

Autologous Fibroblast Technology

Our Approach

Autologous, ex vivo technology to develop novel therapies for skin and connective tissue disorders

Castle Creek Biosciences’ proprietary autologous fibroblast technology is the foundation of our approach for developing personalized, targeted and re-dosable cell-based, gene therapy candidates for monogenic chronic diseases, with an initial focus on skin and connective tissue disorders.

Fibroblasts synthesize extracellular matrix proteins like collagen, which provide structure and support to the skin. Fibroblasts have unique qualifications for localized delivery to gene targets in skin and connective tissues.

This technology was used to develop D-Fi, also known as FCX-007, (dabocemagene autoficel), an autologous gene therapy candidate for the treatment of dystrophic epidermolysis bullosa (DEB)—a devastating progressive, 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, which 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 chronic wounds where the COL7 protein can support the formation of anchoring fibrils in the skin.

A Personalized Approach

Castle Creek Biosciences’ autologous fibroblast technology uses our patented manufacturing process. Small skin biopsies are taken from patients. Their cells are isolated and expanded in culture, transducing the fibroblast cells 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 to active wounds with the goal of expressing the target protein to restore skin integrity. As part of this process, a personalized cell bank of genetically modified autologous fibroblasts is created and cryogenically stored, 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 or any other regulatory agency.