Comparison of PSA-specific CD8+ CTL responses and antitumor immunity generated by plasmid DNA vaccines encoding PSA-HSP chimeric proteins.
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.
Pavlenko
Maxim
M
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
Roos
Anna-Karin
AK
Leder
Christoph
C
Hansson
Lars-Olof
LO
Kiessling
Rolf
R
Levitskaya
Elena
E
Pisa
Pavel
P
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*
D019496:Cancer Vaccines; D006360:Heat-Shock Proteins; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D017430:Prostate-Specific Antigen