Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Induction of immune responses and safety profiles in rhesus macaques immunized with a DNA vaccine expressing human prostate specific antigen

Oncogene volume 20, pages 4497–4506 (2001)Cite this article

Abstract

Prostate specific antigen (PSA) is a widely used marker for prostate cancer, which is secreted by normal prostate cells at low levels, but is produced more substantially by cancer cells. We have previously reported on the use of a DNA vaccine construct that encodes for human PSA gene to elicit host immune responses against cells producing PSA. DNA immunization strategy delivers DNA constructs encoding for a specific immunogen into the host, who becomes the in vivo protein source for the production of antigen. This antigen then is the focus of the resulting immune response. In this study, we examine the induction of immune responses and safety profiles in rhesus macaques immunized with DNA-based PSA vaccine. We observed induction of PSA-specific humoral response as well as positive PSA-specific lymphoproliferative (LPA) response in the vaccinated macaques. We also observed that the stimulated T cells from the PSA-immunized rhesus macaques produced higher levels of Th1 type cytokine IFN-γ than the control vector immunized animals. On the other hand, DNA immunization did not result in any adverse effects in the immunized macaques, as indicated by complete blood counts, leukocyte differentials and hepatic and renal chemistries. The macaques appeared healthy, without any physical signs of toxicity throughout the observation period. In addition, we did not observe any adverse effect on the vaccination site. The apparent safety and immunogenecity of DNA immunization in this study suggest that further evaluation of this vaccination strategy is warranted.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  • Armbruster DA . 1993 Clin. Chem. 39: 181–195

  • Boring CC, Squires TS, Tong T . 1994 Ca: Cancer J. Clin. 44: 7–26

  • Boyer JD, Ugen KE, Wang B, Agadjanyan MG, Gilbert L, Bagarazzi M, Chattergoon M, Frost P, Javadian A, Williams WV, Refaeli Y, Ciccarelli RB, McCallus D, Coney L, Weiner DB . 1997 Nature Med. 3: 526–532

  • Boyer JD, Chattergoon MA, Ugen KE, Shaw A, Bennett M, Cohen A, Nyland S, Lacy K, Bagarazzi ML, Higgins TJ, Baine Y, Ciccarelli RB, Ginsberg RS, MacGregor RR, Weiner DB . 1999 Clin. Immunol. 90: 100–107

  • Clerici M, Lucey DR, Berzofsky JA, Pinto LA, Wynn TA, Blatt SP, Dolan MJ, Hendrix CW, Wolf SF, Shearer GM . 1993 Science 262: 1721–1724

  • Conry RM, LoBuglio AF, Kantor J, Schlom J, Loechel F, Moore SE, Sumerel LA, Barlow DL, Abrams S, Curiel DT . 1994 Cancer Res. 54: 1164–1168

  • Conry RM, White SA, Fultz PN, Khazaeli MB, Stron TV, Allen KO, Barlow DL, Moore SE, Coan PN, Davis I, Curiel DT, LoBuglio AF . 1998 Clin. Cancer Res. 4: 2903–2912

  • D'Amico AV, Whittington R, Kaplan I, Beard C, Schultz D, Malkowicz SB, Wein A, Tomaszewski JE, Coleman CN . 1998 Cancer 82: 334–341

  • Eder JP, Kantoff PW, Roper K, Xu GX, Bubley GJ, Boyden J, Gritz L, Mazzara G, Oh WK, Arlen P, Tsang KY, Panicali D, Schlom J, Kufe DW . 2001 Clin. Cancer Res. 6: 1632–1638

  • Garnick MB, Fair WR . 1998 Sci. Am. 274: 74–83

  • Godley PA . 1999 Cancer Detect. Prev. 23: 316–324

  • Hodge JW, Schlom J, Donohue SJ, Tomaszewski JE, Wheeler CW, Levine BS, Gritz L, Panicali S, Kantor JA . 1995 Int. J. Cancer 63: 231–237

  • Jiao S, Williams P, Berg RK, Hodgeman BA, Liu L, Repetto G, Wolff JA . 1992 Hum. Gene Ther. 3: 21–33

  • Kelley JR, Cole DJ . 1998 Gene Ther. Mol. Biol. 2: 14–30

  • Kim JJ, Nottingham LK, Sin JI, Tsai A, Morrison L, Oh J, Dang K, Hu Y, Kazahaya K, Bennett M, Dentchev T, Wilson DM, Chalian AA, Boyer JD, Agadjanyan MG, Weiner DB . 1998a J. Clin. Invest. 102: 1112–1124

  • Kim JJ, Trivedi NN, Wilson DM, Mahalingam S, Morrison L, Tsai A, Chattergoon MA, Dang K, Patel M, Ahn L, Chalian AA, Boyer JD, Kieber-Emmons T, Agadjanyan MG, Weiner DB . 1998b Oncogene 17: 3125–3135

  • Labrie F, DuPont A, Suburu R, Cusan L, Tremblay M, Gomez JL, Edmond J . 1992 J. Urol. 151: 1283–1290

  • Lekutis C, Shiver JW, Liu MA, Letvin NL . 1997 J. Immunol. 158: 4471–4477

  • Letvin NL, Montefiori DC, Yasutomi Y, Perry HC, Davies M-E, Lekutis C, Alroy M, Freed DC, Lord CI, Handt LK, Liu MA, Shiver JW . 1997 Proc. Natl. Acad. Sci. USA 94: 9378–9383

  • Lotze MT, Shurin M, Davis I, Amoscato A, Storkus WJ . 1997 Adv. Exp. Med. Biol. 417: 551–569

  • MacGregor RR, Boyer JD, Ugen KE, Lacy K, Gluckman S, Bagarazzi ML, Chattergoon M, Baine Y, Higgins TJ, Ciccarelli RB, Coney LR, Ginsberg RS, Weiner DB . 1998 J. Inf. Dis. 178: 92–100

  • Malkowicz SB, Johnson JO . 1998 Hematol. Oncol. Clin. North Am. 12: 649–664

  • Murphy G, Tjoa B, Ragde H, Kenny G, Boynton A . 1996 Prostate 29: 371–380

  • O'Donnell PD, Finan BF . 1989 J. Urol. 142: 1227–1229

  • Porgador A, Snyder D, Gilboa E . 1996 J. Immunol. 156: 2918–2926

  • Rosenberg ES, Billingsley JM, Caliendo AM, Boswell SL, Sax PE, Kalams SA, Walker BD . 1997 Science 278: 1447–1450

  • Sandra MG . 1994 J. Urol. 151: 622–628

  • Seder RA, Paul WE . 1994 Annu. Rev. Immunol. 12: 635–673

  • Small EJ . 1999 Curr. Opin. Oncol. 11: 226–235

  • Smith BF, Baker HJ, Curiel DT, Jiang W, Conry RM . 1998 Gene Ther. 5: 865–868

  • Stenman UH, Leinonen J, Zhang WM, Finne P . 1999 Semin. Cancer Biol. 9: 83–93

  • Tjoa B, Boynton A, Kenny G, Ragde H, Misrock SL, Murphy G . 1996 Prostate 28: 65–69

  • Tuting T, Storkus WJ, Lotze MT . 1997 J. Mol. Med. 75: 478–491

  • Vieweg J, Boczkowski D, Roberson KM, Edwards DW, Philip M, Philip R, Rudoll T, Smith C, Robertson C, Gilboa E . 1994 Cancer Res. 54: 1760–1765

  • Wang MC, Kuriyama M, Papsidero LD, Loor RM, Valenzyela LA, Murphy GP, Chu TM . 1982 Methods Cancer Res. 19: 179–197

  • Wang R, Doolan DL, Le TP, Hedstrom RC, Coonan KM, Charoenvit Y, Jones TR, Hobart P, Margalith M, Ng J, Weiss WR, Sedegah M, de Taisne C, Norman JA, Hoffman SL . 1998 Science 282: 476–480

  • Watt KWK, Lee P-J, M'Timkulu T, Chan W-P, Loor R . 1986 Proc. Natl. Acad. Sci. USA 83: 3166–3170

  • Zagars GK, Pollack A . 1995 Urology 45: 476–483

Download references

Acknowledgements

This work was supported in part by grants from NIH to DB Weiner.

Author information

Authors and Affiliations

  1. Viral Genomix, Inc., Philadelphia, 19104, Pennsylvania, PA, USA

    J Joseph Kim

  2. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, PA, USA

    J Joseph Kim, Joo-Sung Yang, Liesl K Nottingham, Kesen Dang, Darren M Wilson & David B Weiner

  3. Institute of Human Gene Therapy, Philadelphia, 19104, Pennsylvania, PA, USA

    Waixing Tang

  4. Primedica Mason Labs, Worcester, Massachusetts, USA

    Kelledy H Manson & Michael S Wyand

  5. The Wistar Institute, Philadelphia, 19104, Pennsylvania, PA, USA

    David B Weiner

Authors
  1. J Joseph Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joo-Sung Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liesl K Nottingham
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Waixing Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kesen Dang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kelledy H Manson
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Michael S Wyand
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Darren M Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. David B Weiner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David B Weiner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, J., Yang, JS., Nottingham, L. et al. Induction of immune responses and safety profiles in rhesus macaques immunized with a DNA vaccine expressing human prostate specific antigen. Oncogene 20, 4497–4506 (2001). https://doi.org/10.1038/sj.onc.1204542

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204542

Keywords

This article is cited by

Search

Advanced search

Quick links