title: The Telomerase-Derived Anticancer Peptide Vaccine GV1001 as an Extracellular Heat Shock Protein-Mediated Cell-Penetrating Peptide.
abstract: Cell-penetrating peptides (CPPs), which can facilitate the transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular delivery of macromolecules. GV1001, a peptide derived from a reverse-transcriptase subunit of telomerase (hTERT) and developed as a vaccine against various cancers, reportedly has unexpected CPP properties. Unlike typical CPPs, such as the HIV-1 TAT peptide, GV1001 enabled the cytosolic delivery of macromolecules such as proteins, DNA and siRNA via extracellular heat shock protein 90 (eHSP90) and 70 (eHSP70) complexes. The eHSP-GV1001 interaction may have biological effects in addition to its cytosolic delivery function. GV1001 was originally designed as a major histocompatibility complex (MHC) class II-binding cancer epitope, but its CPP properties may contribute to its strong anti-cancer immune response relative to other telomerase peptide-based vaccines. Cell signaling via eHSP-GV1001 binding may lead to unexpected biological effects, such as direct anticancer or antiviral effects. In this review, we focus on the CPP effects of GV1001 bound to eHSP90 and eHSP70.
authors.affiliation: Department of Biomedical Sciences, Microbiology and Immunology, and Liver Research Institute, College of Medicine, Seoul National University, Seoul 03080, Korea. wild0804@snu.ac.kr.
authors.forename: Hong
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Konkuk University School of Medicine, Seoul 05030, Korea. gmreo@naver.com.
authors.forename: Eun-Hye
authors.initials: EH
authors.lastname: Seo
authors.affiliation: Department of Microbiology, Konkuk University School of Medicine, Seoul 05030, Korea. shlee@kku.ac.kr.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, Microbiology and Immunology, and Liver Research Institute, College of Medicine, Seoul National University, Seoul 03080, Korea. kbumjoon@snu.ac.kr.
authors.forename: Bum-Joon
authors.initials: BJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D057846:Cell-Penetrating Peptides / Q000737:chemistry*; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry; D006360:Heat-Shock Proteins / Q000737:chemistry*; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry*; D019098:Telomerase / Q000737:chemistry*; D022223:Vaccines, Subunit / Q000737:chemistry*
chemical_list: D057846:Cell-Penetrating Peptides; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D010446:Peptide Fragments; D022223:Vaccines, Subunit; D019098:Telomerase
keywords: GV1001; cell-penetrating peptides (CPPs); heat shock protein 90; reverse-transcriptase-subunit of telomerase (hTERT)