title: Comparison of PSA-specific CD8+ CTL responses and antitumor immunity generated by plasmid DNA vaccines encoding PSA-HSP chimeric proteins.
abstract: The ability of heat shock proteins (HSPs) to increase the potency of protein- and DNA-based vaccines has been previously reported. We have constructed several plasmid-based vectors encoding chimeric proteins containing prostate-specific antigen (PSA) fused to Mycobacterium tuberculosis hsp70, M. bovis hsp65, Escherichia coli DnaK (hsp70), or human hsp70. Immunizing mice with these plasmids induced CD8+ cytotoxic T lymphocytes (CTLs) specific to human PSA and protected mice from a subsequent subcutaneous challenge with PSA-expressing tumors. We did not observe a significant difference either in the levels of PSA-specific CTLs or in protection against tumor challenge in mice immunized with plasmids expressing PSA-HSP chimeric proteins, as compared to mice receiving a conventional PSA-expressing DNA plasmid. Our data indicate that using HSPs as fusion partners for tumor-specific antigens does not always result in the enhancement of antigen-specific CTL responses when applied in the form of DNA vaccines.
authors.affiliation: Immune and Gene Therapy Laboratory, Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Hospital, R8:01, Stockholm 171 76, Sweden. maxim.pavlenko@cck.ki.se
authors.forename: Maxim
authors.initials: M
authors.lastname: Pavlenko
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Roos
authors.forename: Christoph
authors.initials: C
authors.lastname: Leder
authors.forename: Lars-Olof
authors.initials: LO
authors.lastname: Hansson
authors.forename: Rolf
authors.initials: R
authors.lastname: Kiessling
authors.forename: Elena
authors.initials: E
authors.lastname: Levitskaya
authors.forename: Pavel
authors.initials: P
authors.lastname: Pisa
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids; D017430:Prostate-Specific Antigen / Q000235:genetics* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D006360:Heat-Shock Proteins; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D017430:Prostate-Specific Antigen