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

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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.

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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.

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Authors and Affiliations

  1. Immune and Gene Therapy Laboratory, Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Hospital, R8:01, Stockholm, 171 76, Sweden

    Maxim Pavlenko, Anna-Karin Roos, Christoph Leder, Rolf Kiessling, Elena Levitskaya & Pavel Pisa

  2. Department of Clinical Chemistry, Karolinska Hospital, Stockholm, 171 76, Sweden

    Lars-Olof Hansson

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  1. Maxim Pavlenko
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  2. Anna-Karin Roos
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  3. Christoph Leder
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  6. Elena Levitskaya
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  7. Pavel Pisa
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Correspondence to Maxim Pavlenko.

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Pavlenko, M., Roos, AK., Leder, C. et al. Comparison of PSA-specific CD8+ CTL responses and antitumor immunity generated by plasmid DNA vaccines encoding PSA-HSP chimeric proteins. Cancer Immunol Immunother 53, 1085–1092 (2004). https://doi.org/10.1007/s00262-004-0559-z

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  • DOI: https://doi.org/10.1007/s00262-004-0559-z

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