title: BiVax: a peptide/poly-IC subunit vaccine that mimics an acute infection elicits vast and effective anti-tumor CD8 T-cell responses.
abstract: Therapeutic vaccines for the treatment of cancer are an attractive alternative to some of the conventional therapies that are currently used. More importantly, vaccines could be very useful to prevent recurrences when applied after primary therapy. Unfortunately, most therapeutic vaccines for cancer have performed poorly due to the low level of immune responses that they induce. Previous work done in our laboratory in cancer mouse models demonstrated that vaccines consisting of synthetic peptides representing minimal CD8 T-cell epitopes administered i.v. mixed with poly-IC and anti-CD40 antibodies (TriVax) were capable of inducing massive T cell responses similar to those found during acute infections. We now report that some peptides are capable of inducing similarly large T cell responses after vaccination with poly-IC alone (BiVax). The results show that amphiphilic peptides are more likely to function as strong immunogens in BiVax and that systemic immunizations (i.v. or i.m.) were more effective than local (s.c.) vaccine administration. The immune responses induced by BiVax were found to be effective against established tumors in two mouse cancer models. The roles of various immune-related pathways such as type-I IFN, CD40 costimulation, CD4 T cells, TLRs and the MDA5 RNA helicase were examined. The present findings could facilitate the development of simple and effective subunit vaccines for diseases where CD8 T cells provide a therapeutic benefit.
authors.affiliation: Immunology Program, Moffitt Cancer Center, Tampa, FL 33612, USA.
authors.forename: Hyun-Il
authors.initials: HI
authors.lastname: Cho
authors.forename: Kelly
authors.initials: K
authors.lastname: Barrios
authors.forename: Young-Ran
authors.initials: YR
authors.lastname: Lee
authors.forename: Angelika K
authors.initials: AK
authors.lastname: Linowski
authors.forename: Esteban
authors.initials: E
authors.lastname: Celis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology* / Q000494:pharmacology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000628:therapy*; D050725:Papillomavirus E7 Proteins / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D010455:Peptides / Q000276:immunology*; D011070:Poly I-C / Q000276:immunology*; D014357:Trypsin / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D050725:Papillomavirus E7 Proteins; D010446:Peptide Fragments; D010455:Peptides; C059731:oncogene protein E7, Human papillomavirus type 16; C489303:PRSS1 protein, human; D014357:Trypsin; D011070:Poly I-C