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 Article
  • Published:

Breast Cancer

Clinical outcome of breast and ovarian cancer patients treated with high-dose chemotherapy, autologous stem cell rescue and THERATOPE® STn-KLH cancer vaccine

Bone Marrow Transplantation volume 25, pages 1233–1241 (2000)Cite this article

Abstract

The purpose of this study was to evaluate the toxicity and potential efficacy of administering the THERATOPE® STn-KLH cancer vaccine to ovarian and breast cancer patients after an autologous stem cell transplant. Forty patients (11 high-risk stage II/III breast cancer, 22 stage IV breast cancer, and seven stage III/IV ovarian cancer patients) were treated with high-dose chemotherapy followed by autologous/syngeneic stem cell rescue and vaccination with THERATOPE STn-KLH (Sialyl-Tn-KLH with Detox-B Stable Emulsion). Each patient was scheduled to receive a total of five vaccinations beginning on days 30–151 after stem cell infusion. The vaccine was well tolerated. Induration and erythema at the site of injection were the most common side-effects. When one compares the outcome of patients vaccinated with 66 breast and ovarian cancer patients who were not, following risk-adjustment analysis, vaccinated patients appeared more likely to survive (P = 0.07) and less likely to relapse (P = 0.10). Vaccinated patients with the greatest specific lytic activity against STn+OVCAR tumor cells relative to nonspecific killing of Daudi cells tended to remain in remission longer than patients who displayed less specific immune activity (P = 0.057). We conclude that the THERATOPE STn-KLH cancer vaccine is well tolerated in breast and ovarian cancer patients after autologous transplant and, while not statistically significant, the trends in data support the concept that THERATOPE vaccine may decrease the risk for relapse and death and thus warrants further study. Bone Marrow Transplantation (2000) 25, 1233–1241.

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

Similar content being viewed by others

References

  1. Stiff PJ, Bayer R, Kerger C et al. High-dose chemotherapy with autologous transplantation for persistent/relapsed ovarian cancer: a multivariate analysis of survival for 100 consecutively treated patients J Clin Oncol 1997 15: 1309–1317

    Article  CAS  Google Scholar 

  2. Holmberg LA, Demirer T, Rowley S et al. High-dose busulfan, melphalan and thiotepa followed by autologous peripheral blood stem cell (PBSC) rescue in patients with advanced stage III/IV ovarian cancer Bone Marrow Transplant 1998 22: 651–659

    Article  CAS  Google Scholar 

  3. Antman KH, Rowlings PA, Vaughan WP et al. High-dose chemotherapy with autologous hematopoietic stem-cell support for breast cancer in North America J Clin Oncol 1997 15: 1870–1879

    Article  CAS  Google Scholar 

  4. Bensinger WI, Schiffman KS, Holmberg L et al. High-dose busulfan, melphalan, thiotepa and peripheral blood stem cell infusion for the treatment of metastatic breast cancer Bone Marrow Transplant 1997 19: 1183–1189

    Article  CAS  Google Scholar 

  5. Brenner MK, Rill DR, Moen RC et al. Gene-marking to trace origin of relapse after autologous bone-marrow transplantation Lancet 1993 341: 85–86

    Article  CAS  Google Scholar 

  6. Borges E, Wiesmuller KH, Jung G, Walden P . Efficacy of synthetic vaccines in the induction of cytotoxic T lymphocytes. Comparison of the costimulating support provided by helper T cells and lipoamino acid J Immunol Meth 1994 173: 253–263

    Article  CAS  Google Scholar 

  7. Cormier JN, Salgaller ML, Prevette T et al. Enhancement of cellular immunity in melanoma patients immunized with a peptide from MART-1/Melan A Cancer J Sci Am 1997 3: 37–44

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Kantor J, Irvine K, Abrams S et al. Antitumor activity and immune responses induced by a recombinant carcinoembryonic antigen-vaccinia virus vaccine J Natl Cancer Inst 1992 84: 1084–1091

    Article  CAS  Google Scholar 

  9. Tsang KY, Zaremba S, Nieroda CA et al. Generation of human cytotoxic T cells specific for human carcinoembryonic antigen epitopes from patients immunized with recombinant vaccinia-CEA vaccine J Natl Cancer Inst 1995 87: 982–990

    Article  CAS  Google Scholar 

  10. Livingston PO, Wong GY, Adluri S et al. Improved survival in stage III melanoma patients with GM2 antibodies: a randomized trial of adjuvant vaccination with GM2 ganglioside J Clin Oncol 1994 12: 1036–1044

    Article  CAS  Google Scholar 

  11. MacLean GD, Reddish M, Koganty RR et al. Immunization of breast cancer patients using a synthetic sialyl-Tn glycoconjugate plus Detox adjuvant Cancer Immunol Immunother 1993 36: 215–222

    Article  CAS  Google Scholar 

  12. Longenecker BM, Reddish M, Koganty R, MacLean GD . Immune responses of mice and human breast cancer patients following immunization with synthetic sialyl-Tn conjugated to KLH plus detox adjuvant Ann NY Acad Sci 1993 690: 276–291

    Article  CAS  Google Scholar 

  13. MacLean GD, Reddish MA, Koganty RR, Longenecker BM . Antibodies against mucin-associated sialyl-Tn epitopes correlate with survival of metastatic adenocarcinoma patients undergoing active specific immunotherapy with synthetic STn vaccine J Immunother Emph Tumor Immunol 1996 19: 59–68

    Article  CAS  Google Scholar 

  14. MacLean GD, Miles DW, Rubens RD et al. Enhancing the effect of THERATOPE STn-KLH cancer vaccine in patients with metastatic breast cancer by pretreatment with low-dose intravenous cyclophosphamide J Immunother Emph Tumor Immunol 1996 19: 309–316

    Article  CAS  Google Scholar 

  15. Longenecker BM, Reddish M, Miles D, MacLean GD . Synthetic tumor-associated sialyl-Tn antigen as an immunotherapeutic cancer vaccine Vaccine Res 1993 2: 151–162

    CAS  Google Scholar 

  16. Thor A, Ohuchi N, Szpak CA et al. Distribution of oncofetal antigen tumor-associated glycoprotein-72 defined by monoclonal antibody B72.3 Cancer Res 1986 46: 3118–3124

    CAS  PubMed  Google Scholar 

  17. Reddish MA, Jackson L, Koganty RR et al. Specificities of anti-sialyl-Tn and anti-Tn monoclonal antibodies generated using novel clustered synthetic glycopeptide epitopes Glycoconj J 1997 14: 549–560

    Article  CAS  Google Scholar 

  18. Kobayashi H, Terao T, Kawashima Y . Serum sialyl Tn as an independent predictor of poor prognosis in patients with epithelial ovarian cancer J Clin Oncol 1992 10: 95–101

    Article  CAS  Google Scholar 

  19. Federici MF, Kudryashov V, Saigo PE et al. Selection of carbohydrate antigens in human epithelial ovarian cancers as targets for immunotherapy: serous and mucinous tumors exhibit distinctive patterns of expression Int J Cancer 1999 81: 193–198

    Article  CAS  Google Scholar 

  20. Ryuko K, Iwanari O, Kitao M, Moriwaki S . Immunohistochemical evaluation of sialosyl-Tn antigens in various ovarian carcinomas Gynecol Oncol 1993 49: 215–224

    Article  CAS  Google Scholar 

  21. Inoue M, Ton SM, Ogawa H, Tanizawa O . Expression of Tn and sialyl-Tn antigens in tumor tissues of the ovary Am J Clin Pathol 1991 96: 711–716

    Article  CAS  Google Scholar 

  22. Miles DW, Happerfield LC, Smith P et al. Expression of sialyl-Tn predicts the effect of adjuvant chemotherapy in node-positive breast cancer Br J Cancer 1994 70: 1272–1275

    Article  CAS  Google Scholar 

  23. Reddish MA, MacLean GD, Poppema S et al. Pre-immunotherapy serum CA27.29 (MUC-1) mucin level and CD69+ lymphocytes correlate with effects of Theratope sialyl-Tn-KLH cancer vaccine in active specific immunotherapy Cancer Immunol Immunother 1996 42: 303–309

    Article  CAS  Google Scholar 

  24. Yacyshyn MB, Poppema S, Berg A et al. CD69+ and HLA-DR+ activation antigens on peripheral blood lymphocyte populations in metastatic breast and ovarian cancer patients: correlations with survival following active specific immunotherapy Int J Cancer 1995 61: 470–474

    Article  CAS  Google Scholar 

  25. Miles DW, Towlson KE, Graham R et al. A randomised phase II study of sialyl-Tn and DETOX-B adjuvant with or without cyclophosphamide pretreatment for the active specific immunotherapy of breast cancer Br J Cancer 1996 74: 1292–1296

    Article  CAS  Google Scholar 

  26. MacLean GD, Samuel J, Meikle A et al. Active immunization of human ovarian cancer patients against a common carcinoma (Thomsen–Friedenreich) determinant using a synthetic carbohydrate antigen J Immunother 1992 11: 292–305

    Article  CAS  Google Scholar 

  27. Henningsson CM, Selvaras S, MacLean GD et al. T cell recognition of a tumor-associated glycoprotein and its synthetic carbohydrate epitopes: stimulation of anticancer T cell immunity in vivo Cancer Immunol Immunother 1987 25: 231–241

    Article  CAS  Google Scholar 

  28. Galli-Stampino L, Meinjohanns E, Frische K et al. T-cell recognition of tumor-associated carbohydrates: the nature of the glycan moiety plays a decisive role in determining glycopeptide immunogenicity Cancer Res 1997 57: 3214–3222

    CAS  PubMed  Google Scholar 

  29. Agrawal B, Krantz MJ, Reddish MA, Longenecker BM . Cancer-associated MUC1 mucin inhibits human T-cell proliferation, which is reversible by IL-2 Nature Med 1998 4: 43–49

    Article  CAS  Google Scholar 

  30. Storek J, Witherspoon RP . Immunological reconstitution after hemopoietic stem cell transplantation. In: Atkinson K (ed) Clinical Bone Marrow and Blood Stem Cell Transplantation: A Reference Textbook Cambridge University Press: Cambridge, UK 2000 111–146

    Google Scholar 

  31. Sandmaier BM, Oparin DV, Holmberg LA et al. Evidence of a cellular immune response against sialyl-Tn in breast and ovarian cancer patients after high-dose chemotherapy, stem cell rescue, and immunization with theratope STn-KLH cancer vaccine J Immunother 1999 22: 54–66

    Article  CAS  Google Scholar 

  32. Gutierrez-Delgado F, Holmberg L, Maloney D et al. High-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) as consolidation for noninflammatory high-risk (HR) breast cancer Program/Proceedings of American Society of Clinical Oncology, 35th Annual Meeting 1999 18: 83a (Abstr.)

    Google Scholar 

  33. Barra A, Cordonnier C, Preziosi MP et al. Immunogenicity of Haemophilus influenzae type b conjugate vaccine in allogeneic bone marrow recipients J Infect Dis 1992 166: 1021–1028

    Article  CAS  Google Scholar 

  34. Witherspoon RP, Matthews D, Storb R et al. Recovery of in vivo cellular immunity after human marrow grafting: influence of time postgrafting and acute graft-versus-host disease Transplantation 1984 37: 145–150

    Article  CAS  Google Scholar 

  35. Atkinson K . Reconstruction of the haemopoietic and immune systems after marrow transplantation (review) Bone Marrow Transplant 1990 5: 209–226

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported in part by grants CA67112 and CA66186 from the National Cancer Institute, National Institutes of Health, DHHS, Bethesda, MD, USA, and by The Jose Carreras Foundation Against Leukemia. We thank Erlinda B Santos for technical assistance and the Autologous Transplant Team at the Fred Hutchinson Cancer Research Center, Seattle, WA, for providing the patient care. We are also grateful to Helen Crawford and Bonnie Larson for their assistance in manuscript preparation.

Author information

Author notes

  1. MA Reddish

    Present address: ID Vaccine, Bothell, WA, USA

Authors and Affiliations

  1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    LA Holmberg, DV Oparin, T Gooley, K Lilleby, W Bensinger & BM Sandmaier

  2. Clinical Research Division, University of Washington School of Medicine, Seattle, WA, USA

    LA Holmberg, T Gooley, W Bensinger & BM Sandmaier

  3. Biomira Inc, Edmonton, Alberta, Canada

    MA Reddish, GD MacLean & BM Longenecker

Authors
  1. LA Holmberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. DV Oparin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T Gooley
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K Lilleby
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. W Bensinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. MA Reddish
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. GD MacLean
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. BM Longenecker
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. BM Sandmaier
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Holmberg, L., Oparin, D., Gooley, T. et al. Clinical outcome of breast and ovarian cancer patients treated with high-dose chemotherapy, autologous stem cell rescue and THERATOPE® STn-KLH cancer vaccine. Bone Marrow Transplant 25, 1233–1241 (2000). https://doi.org/10.1038/sj.bmt.1702430

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1702430

Keywords

This article is cited by

Search

Advanced search

Quick links