Scientists in the laboratory of associate professor Laszlo Otvos Jr., Ph.D., have spent several years studying an insect-derived antimicrobial peptide called pyrrhocoricin. Both pyrrhocoricin in its native state and lab-created analogs are capable of entering and killing a number of strains of bacteria, including E. coli. Initially interested in pyrrhocoricin and its analogs because of their antimicrobial properties, Otvos and his research team are now exploring whether these peptides could be employed as delivery vehicles for other peptide or peptide-based drugs that would not normally be able to penetrate mammalian cell membranes and tissues.
In their study, published online today in Molecular Pharmaceutics, the researchers showed that native pyrrhocoricin can penetrate human dendritic cells, an important type of immune cell, and that the designer pyrrhocoricin analog can penetrate both dendritic cells and fibroblasts, a cell that produces the collagen fibers that make up connective tissue. The dendritic cells displayed signs of stimulation, which opens the question of whether this peptide delivery system could be used to create new vaccines or immune therapies. The paper will appear in the print edition of the journal in May.
"Our results suggest that our designed pyrrhocoricin analogs are good candidates for transporting peptidic cargo across cell membranes in general, and for potential use in therapeutic applications as well as in vaccine development," Otvos says.
Dendritic cells are a type of antigen-presenting cell, which shows antigen on its surface to T cells to prompt an immune system response. Researchers have been exploring whether peptide-based vaccines can induce effective T cell responses, particularly in cancers.
Otvos's research is early-stage, and it remains to be seen whether his designer antimicrobial peptide analogs will be useful in activating dendritic cells as part of an immune therapy. He continues to explore both its general use as a drug-delivery vehicle and its specific use in activating the immune system in future studies.
With Otvos, the co-authors of the paper are: Mare Cudic, formerly of Wistar and Chaperone Technologies, and Brendon Y. Chua, Georgia Deliyannis, and David C. Jackson, all of the University of Melbourne, Australia. Funding for the research was provided by the Commonwealth Universal Research Enhancement Program, Pennsylvania Department of Health, and the National Health and Medical Research Council of Australia.
The Wistar Institute is an independent nonprofit biomedical research institution dedicated to discovering the causes and cures for major diseases, including cancer, cardiovascular disease, autoimmune disorders, and infectious diseases. Founded in 1892 as the first institution of its kind in the nation, The Wistar Institute today is a National Cancer Institute-designated Cancer Center - one of only eight focused on basic research. Discoveries at Wistar have led to the development of vaccines for such diseases as rabies and rubella, the identification of genes associated with breast, lung, and prostate cancer, and the development of monoclonal antibodies and other significant research technologies and tools.
News releases from The Wistar Institute are available to reporters by direct e-mail or fax upon request. They are also posted electronically to Wistar's home page (http://www.wistar.upenn.edu), and to EurekAlert! (http://www.eurekalert.org), an Internet resource sponsored by the American Association for the Advancement of Science.
Journal
Molecular Pharmaceutics