Department of Dermatology

Cutaneous Immunobiology and Genetic Immunization

In studies published in the journals Nature Medicine and Gene Therapy, Department investigators demonstrated that a novel genetic immunization strategy which utilizes a gene gun can be used to effectively transfect dendritic cells in human skin in vivo, resulting in the induction of potent immune responses. The ability to transfect dendritic cells offers considerable opportunity for immune manipulation, with potential practical applications for the treatment of cancer, infectious diseases, and autoimmune disease. This technology is now being evaluated in clinical trials and is also described in the The Pittsburgh Post-Gazette article “These Gold Bullets Help Target Attack on Cancer.”

In pioneering studies published in the journal Nature Immunology, Department investigators describe the discovery of a precursor cell in skin that has the potential to point the way to manipulating the immune system. This accomplishment has broad implications for the future development of immunotherapies designed to prevent or treat a variety of cancers, as well as the development of immunotherapies designed to treat autoimmune mediated diseases and facilitate transplantation. In addition this discovery is likely to have significant impact on the development of tissue engineering, particularly in the development of engineered human skin. This discovery is summarized in the Pittsburgh Post-Gazette article "Under Your Skin.”

References

  • Condon, C, Watkins, S, Celluzzi C., Thompson, K.M, and Falo, LD, Jr. DNA-based immunization by in vivo transfection of dendritic cells. Nature Medicine 2(10): 1996. ABSTRACT
  • Falo LD Jr. Targeting the Skin for Genetic Immunization. Proceedings of the Association of American Physicians. 111(3): 211-9. 1999. ABSTRACT
  • Larregina AT and Falo, LD, Jr. Generating and regulating immune responses through cutaneous gene therapy. Human Gene Therapy, 11:2301-2305, 2000. ABSTRACT
  • Larregina AE, Stolinski, L., Watkins SC, Storkus WJ and Falo, LD. Jr. Transfection and Activation of Dendritic Cells in Human Skin. Gene Therapy 8:608-617. 2001. ABSTRACT
  • Larregina, Adriana T., Morelli, Adrian E., Spencer, Lori A., Logar, Alison J., Watkins, Simon C., Thomson, Angus W. and Falo, L D., Jr. Dermal-resident CD14+ cells differentiate into Langerhans cells. Nature Immunology, 12, 1151-1158. 2001. ABSTRACT
  • Larregina AE, Stolinski, L., Watkins SC, Storkus WJ and Falo, LD. Jr. Transfection and Activation of Dendritic Cells in Human Skin. Gene Therapy 8:608-617. 2001. ABSTRACT
  • Morel PA, Falkner D, Plowey J, Larregina AT and Falo LD, Jr. DNA immunization: altering the cellular localisation of expressed protein and the immunisation route allows manipulation of the immune response, Vaccine, In Press, 2003. 
  • Larregina AT, Morelli AE, Tkacheva OErdos G, Donahue C, Watkins SC, Thomson AW, and Falo, LD, Jr. Highly efficient expression of transgenic proteins by naked DNA transfected dendritic cells through terminal differentiation. Blood, 10.1182/blood-2003-02-0524. 2003. ABSTRACT