Author Interviews, Cancer Research, JAMA, Vaccine Studies / 27.05.2014
Cancer Vaccine Development: Using Synthetic Peptides to Penetrate Cell Membrane
MedicalResearch.com Interview with:
Scott A. Gruber, M.D., Ph.D., MBA, FACS, FCP, FACHE, CPE
Chief of Staff, John D. Dingell VA Medical Center
Associate Dean for Veterans Affairs & Professor of Surgery
Wayne State University School of Medicine
John D. Dingell VA Medical Center Chief of Staff
Detroit, MI 48201
MedicalResearch: What are the main findings of the study?
Dr. Gruber: We successfully addressed the problem of inadequate intracellular delivery of tumor- specific antigens (TSAs) to dendritic cells (DCs) by using synthetic cell-penetrating domains or peptides (CPPs) to create fusion tumor antigens (Ags) that readily penetrate through the plasma membrane. We demonstrated cloning and purification of the TSA melanoma-associated antigen 3 (MAGE-A3) in frame with CPP, producing enhanced cytosolic bioavailability in dendritic cells without altering cell functionality. Further, we showed that recombinant bacterial proteins can be easily engineered to purify large amounts of CPP-MAGE-A3. Use of full-length proteins circumvents the need to define HLA class I allele binding before vaccination and increases the number of epitopes recognized by CD8+ cytotoxic T lymphocytes (CTLs) when compared with peptide-pulsed dendritic cells. Finally, the use of proteins rather than plasmids or viral vectors for in vitro dendritic cell vaccine preparation avoids the practical and theoretical safety concerns regarding genomic modification.
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