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Immuntherapie gynäkologischer Malignome

Immunotherapy of gynecological malignant tumors

  • Leitthema
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Der Onkologe Aims and scope

Zusammenfassung

Immuntherapien sind aufgrund der häufig geringen Tumorlast nach Primärtherapie und der fehlenden Kreuzresistenz zu etablierten Verfahren eine attraktive Option zur Verbesserung der Therapie gynäkologischer Malignome. Beispiele sind die Etablierung des monoklonalen Antikörpers Trastuzumab beim Mammakarzinom und die erfolgreiche HPV-basierte Impfung zur Prävention des Zervixkarzinoms. Dieser Beitrag stellt die präklinischen und klinischen Erfahrungen mit passiven und aktiven Immunisierungsstrategien beim Ovarial-, Zervix- und Mammakarzinom vor.

Abstract

Immunotherapeutic approaches are attractive treatment options for gynecological malignancies, due to the frequently low tumor burden after primary therapies and the lack of cross-resistance with standard therapies. Examples are the establishment of the monoclonal antibody trastuzumab for the therapy of metastatic breast cancer and the successful HPV-based vaccination for the prevention of HPV-associated cervical cancer. This review describes preclinical and clinical experiences with passive and active immunization in ovarian, cervical and breast cancers.

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Literatur

  1. Edwards RP, Gooding W, Lembersky BC, Colonello K, Hammond R, Paradise C, Kowal CD, Kunschner AJ, Baldisseri M, Kirkwood JM, Berman RB (1997) Comparison of toxicity and survival following intraperitoneal recombinant interleukin-2 for persistent ovarian cancer after platinum: twenty-four-hour versus 7-day infusion. J Clin Oncol 15:3399–3407

    Google Scholar 

  2. Windbichler GH, Hausmaninger H, Stummvoll W, Graf AH, Kainz C, Lahodny J, Denison U, Muller-Holzner E, Marth C (2000) Interferon-gamma in the first-line therapy of ovarian cancer: a randomized phase III trial. Br J Cancer 82:1138–1144

    Google Scholar 

  3. Hall GD, Brown JM, Coleman RE, Stead M, Metcalf KS, Peel KR, Poole C, Crawford M, Hancock B, Selby PJ, Perren TJ (2004) Maintenance treatment with interferon for advanced ovarian cancer: results of the Northern and Yorkshire gynaecology group randomised phase III study. Br J Cancer 91:621–626

    Google Scholar 

  4. Nicholson S, Bomphray CC, Thomas H, McIndoe A, Barton D, Gore M, George AJ (2004) A phase I trial of idiotypic vaccination with HMFG1 in ovarian cancer. Cancer Immunol Immunother 53:809–816

    Google Scholar 

  5. Qian F, Gnjatic S, Jager E, Santiago D, Jungbluth A, Grande C, Schneider S, Keitz B, Driscoll D, Ritter G, Lele S, Sood A, Old LJ, Odunsi K (2004) Th1/Th2 CD4+ T cell responses against NY-ESO-1 in HLA-DPB1*0401/0402 patients with epithelial ovarian cancer. Cancer Immun 4:12

    Google Scholar 

  6. Disis ML, Gooley TA, Rinn K, Davis D, Piepkorn M, Cheever MA, Knutson KL, Schiffman K (2002) Generation of T-cell immunity to the HER-2/neu protein after active immunization with HER-2/neu peptide-based vaccines. J Clin Oncol 20(11):2624–2632

    Article  CAS  PubMed  Google Scholar 

  7. Holmberg LA, Oparin DV, Gooley T, Sandmaier BM (2003) The Role of Cancer Vaccines Following Autologous Stem Cell Rescue in Breast and Ovarian Cancer Patients: Experience with the STn-KLH Vaccine (Theratope(R). Clin Breast Cancer 3 (Suppl 4):144–151

    Google Scholar 

  8. Schlienger K, Chu CS, Woo EY, Rivers PM, Toll AJ, Hudson B, Maus MV, Riley JL, Choi Y, Coukos G, Kaiser LR, Rubin SC, Levine BL, Carroll RG, June CH (2003): TRANCE- and CD40 ligand-matured dendritic cells reveal MHC class I-restricted T cells specific for autologous tumor in late-stage ovarian cancer patients. Clin Cancer Res 9:1517–1527

    Google Scholar 

  9. Brossart P, Wirths S, Stuhler G, Reichardt VL, Kanz L, Brugger W (2000) Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells. Blood 96:3102–3108

    CAS  PubMed  Google Scholar 

  10. Gong J, Nikrui N, Chen D, Koido S, Wu Z, Tanaka Y, Cannistra S, Avigan D, Kufe D (2000) Fusions of human ovarian carcinoma cells with autologous or allogeneic dendritic cells induce antitumor immunity. J Immunol 165:1705–1711

    Google Scholar 

  11. Kim DK, Lee TV, Castilleja A, Anderson BW, Peoples GE, Kudelka AP, Murray JL, Sittisomwong T, Wharton JT, Kim JW, Ioannides CG (1999) Folate binding protein peptide 191–199 presented on dendritic cells can stimulate CTL from ovarian and breast cancer patients. Anticancer Res 19(4B):2907–2916

    Google Scholar 

  12. Berek JS, Taylor PT, Gordon A, Cunningham MJ, Finkler N, Orr J Jr, Rivkin S, Schultes BC, Whiteside TL, Nicodemus CF (2004) Randomized, placebo-controlled study of oregovomab for consolidation of clinical remission in patients with advanced ovarian cancer. J Clin Oncol 22:3507–1516

    Google Scholar 

  13. Reinartz S, Kohler S, Schlebusch H, Krista K, Giffels P, Renke K, Huober J, Mobus V, Kreienberg R, DuBois A, Sabbatini P, Wagner U (2004) Vaccination of patients with advanced ovarian carcinoma with the anti-idiotype ACA125: immunological response and survival (phase Ib/II). Clin Cancer Res 10:1580–1587

    Google Scholar 

  14. Bookman MA, Darcy KM, Clarke-Pearson D, Boothby RA, Horowitz IR (2003) Evaluation of monoclonal humanized anti-HER2 antibody, trastuzumab, in patients with recurrent or refractory ovarian or primary peritoneal carcinoma with overexpression of HER2: a phase II trial of the Gynecologic Oncology Group. J Clin Oncol 21:283–290

    Google Scholar 

  15. Jaeger M, Stroehlein MA, Schoberth A, Burges A, Heiss MM, Lindhofer H (2004) Immunotherapy with the trifunctional antibody removab leads to significant elimination of tumor cells from malignant ascites in ovarian cancer: Results of a phase I/II study. Proc Annu Meet Am Soc Clin Oncol 22:2504 (Abstract)

    Google Scholar 

  16. Seiden M, Benigno BB, The SMART study investigator group (2004) A pivotal phase III trial to evaluate the efficacy and safety of adjuvant treatment with R1549 (yttrium-90-labeled HMFG1 murine monoclonal antibody) in epithelial ovarian cancer. Proc Annu Meet Am Soc Clin Oncol 22:5008 (Abstract)

    Google Scholar 

  17. Johnson DA, Briggs SL, Gutowski MC, Barton R (1995) Anti-tumor activity of CC49-doxorubicin immunoconjugates. Anticancer Res 15:1387–1393

    Google Scholar 

  18. Harper DM, Franco EL, Wheeler C, Ferris DG, Jenkins D, Schuind A, Zahaf T, Innis B, Naud P, De Carvalho NS, Roteli-Martins CM, Teixeira J, Blatter MM, Korn AP, Quint W, Dubin G (2004) Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 364:1757–1765

    Google Scholar 

  19. Koutsky LA, Ault KA, Wheeler CM, Brown DR, Barr E, Alvarez FB, Chiacchierini LM, Jansen KU; Proof of Principle Study Investigators (2002) A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 347:1645–1651

    Article  CAS  PubMed  Google Scholar 

  20. Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, Slamon DJ, Murphy M, Novotny WF, Burchmore M, Shak S, Stewart SJ, Press M (2002) Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20:719–726

    Article  PubMed  Google Scholar 

  21. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783–792

    Article  CAS  PubMed  Google Scholar 

  22. Buzdar AU, Hunt K, Smith T, Francis D, Ewer M, Booser D, Singletary E, Buchholz T, Sahin A, Hortobagyi GN (2004) Significantly higher pathological complete remission (PCR) rate following neoadjuvant therapy with trastuzumab (H), paclitaxel (P), and anthracycline-containing chemotherapy (CT): Initial results of a randomized trial in operable breast cancer (BC) with HER/2 positive disease. Proc Annu Meet Am Soc Clin Oncol 22:520 (Abstract)

    Google Scholar 

  23. Repp R, van Ojik HH, Valerius T, Groenewegen G, Wieland G, Oetzel C, Stockmeyer B, Becker W, Eisenhut M, Steininger H, Deo YM, Blijham GH, Kalden JR, van de Winkel JG, Gramatzki M (2003) Phase I clinical trial of the bispecific antibody MDX-H210 (anti-FcgammaRI x anti-HER-2/neu) in combination with Filgrastim (G-CSF) for treatment of advanced breast cancer. Br J Cancer 89:2234–2243

    Google Scholar 

  24. Miller KD, Rugo HS, Cobleigh MA (2002) Phase III trial of capecitabine (Xeloda) and bevacizumab (Avastin) versus capecitabine alone in women with metastatic breast cancer previously treated with an anthracycline and a taxane. Breast Cancer Res Treat 76 (Suppl 1):37

    Google Scholar 

  25. Reddish M, MacLean GD, Koganty RR, Kan-Mitchell J, Jones V, Mitchell MS, Longenecker BM (1998) Anti-MUC1 class I restricted CTLs in metastatic breast cancer patients immunized with a synthetic MUC1 peptide. Int J Cancer 76:817–823

    Article  CAS  PubMed  Google Scholar 

  26. Sandmaier BM, Oparin DV, Holmberg LA, Reddish MA, MacLean GD, Longenecker BM (1999) 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 22:54–66

    Google Scholar 

  27. Ibrahim NK, Murray J,Parker J, Finke L, Miles D, Theratope Study Group (2004) Humoral immune-response to naturally occurring STn in metastatic breast cancer patients (MBC pts) treated with STn-KLH vaccine. Proc Annu Meet Am Soc Clin Oncol 22:2547 (Abstract)

    Google Scholar 

  28. Avigan D, Vasir B, Gong J, Borges V, Wu Z, Uhl L, Atkins M, Mier J, McDermott D, Smith T, Giallambardo N, Stone C, Schadt K, Dolgoff J, Tetreault JC, Villarroel M, Kufe D (2004) Fusion cell vaccination of patients with metastatic breast and renal cancer induces immunological and clinical responses. Clin Cancer Res 10(14):4699–4708

    Google Scholar 

  29. Svane IM, Pedersen AE, Johnsen HE, Nielsen D, Kamby C, Gaarsdal E, Nikolajsen K, Buus S, Claesson MH (2004) Vaccination with p53-peptide-pulsed dendritic cells, of patients with advanced breast cancer: report from a phase I study. Cancer Immunol Immunother 53:633–641

    Google Scholar 

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Authors and Affiliations

  1. Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Kiel

    F. Hilpert, J. Pfisterer & W. Jonat

  2. Institut für Immunologie, Universitätsklinikum Schleswig-Holstein, Campus Kiel

    A. Heiser & D. Kabelitz

  3. Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Michaelisstraße 16, 24105 , Kiel

    F. Hilpert

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  1. F. Hilpert
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  2. A. Heiser
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  3. D. Kabelitz
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  4. J. Pfisterer
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  5. W. Jonat
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Correspondence to F. Hilpert.

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Hilpert, F., Heiser, A., Kabelitz, D. et al. Immuntherapie gynäkologischer Malignome. Onkologe 11, 530–535 (2005). https://doi.org/10.1007/s00761-005-0867-8

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  • DOI: https://doi.org/10.1007/s00761-005-0867-8

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