An epidermal biosensor is a novel concept in tissue engineering in which a skin graft acts as a continuous monitor for the presence of a disease- associated molecules in a patient's circulation. An inflammatory response, manifest as erythema at the site of the epidermal biosensor, provides the patient with an early warning of onset of disease. An epidermal biosensor would be particularly valuable to patients with known risk factors for specific of cancers. The goal of the research proposed here is to develop a prototype epidermal biosensor. We plan to genetically engineer normal human keratinocytes to express chimeric receptors and test their function in vitro. A single chain Fv (scFv) antibody with high affinity to carcinoembryonic antigen (CEA) will serve as the ligand binding domain of the chimeric receptor. The intracellular domain is designed to initiate signal transduction resulting in a proinflammatory response. Keratinocytes transfected with a chimeric receptor will be tested for capacity to bind CEA and respond by producing and secreting inflammatory cytokines. In future studies (phase II - not described here), the modified keratinocytes will be grown into a stratified epidermis in vitro, transplanted onto experimental animals. The function of the graft as an epiderma1 biosensor will be tested in vivo. PROPOSED COMMERCIAL APPLICATIONS: Screening holds the potential to detect cancer in patients at risk because of genetic predisposition or previous disease. Research shows better outcomes after early detection. If a reliable method were available for early detection, the market would be large, since there are 1.2 million new cancer cases in the US every year. Epidermal biosensors have potential beyond early cancer detect as continuous, in vivo monitors for other disease states and exposure to toxic substances
