TY - JOUR

T1 - Comparison of PSA-specific CD8+ CTL responses and antitumor immunity generated by plasmid DNA vaccines encoding PSA-HSP chimeric proteins

AU - Pavlenko, Maxim

AU - Roos, Anna-Karin

AU - Leder, Christoph

AU - Hansson, L.O.

AU - Kiessling, Rolf

AU - Levitskaya, Elena

AU - Pisa, Pavel

N1 - Funding Information: Acknowledgements We thank Mr W David Culp Jr and Ms Ashley Miller for the critical assistance with preparation of the manuscript. This study was supported by the Cancer Society in Stockholm, the Swedish Cancer Society, Karolinska Institute Funds, Swedish Research Council, Wallenberg’s Foundation, and Swedish Society for Medical Research.

PY - 2004/12

Y1 - 2004/12

N2 - 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.

AB - 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.

KW - Biology

KW - CTL

KW - DNA vaccine

KW - heat shock protein

KW - prostate-specific antigen

UR - http://www.scopus.com/inward/record.url?scp=8644277992&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/6ef4a9e9-90c2-3136-9988-9e2dd5b1c4fa/

U2 - 10.1007/s00262-004-0559-z

DO - 10.1007/s00262-004-0559-z

M3 - Journal articles

VL - 53

SP - 1085

EP - 1092

JO - Cancer Immunology, Immunotherapy

JF - Cancer Immunology, Immunotherapy

SN - 1432-0851

IS - 12

ER -