Download PDF
TumorDiagnostik & Therapie 2005; 26(6): 258-266
DOI: 10.1055/s-2005-858952
Thieme Onkologie Aktuell

© Georg Thieme Verlag Stuttgart · New York

Vakzinetherapie des Prostatakarzinoms

Vaccine Therapy of Prostate CancerC. Doehn1 , T. Böhmer1 , M. Sommerauer1 , I. Kausch1 , D. Jocham1
  • 1Klinik und Poliklinik für Urologie, Universitätsklinikum Schleswig-Holstein (UKSH), Campus Lübeck
Further Information

Publication History

Publication Date:
09 December 2005 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Die Vakzinetherapie des Prostatakarzinoms unter Studienbedingungen hat erst in den letzten Jahren an Bedeutung gewonnen. Die verschiedenen Vakzinetechniken sind sehr variabel und werden in erster Linie bei Patienten mit fortgeschrittenem Prostatakarzinom und nach Versagen einer antihormonellen Therapie eingesetzt. In der vorliegenden Übersichtsarbeit werden Vakzinetechniken mit Tumorzellen, mit dendritischen Zellen oder mit Pockenviren analysiert. Für diese Ansätze sind Studien der Phase-III geplant, begonnen oder sogar abgeschlossen. Viele Studien zeigen eine Effektivität im Hinblick auf die Endpunkte einer Immunantwort und/oder biochemischem und/oder klinischem Ansprechen. Kürzlich konnte sogar für eine Vakzine mit autologen dendritischen Zellen gezeigt werden, dass es gegenüber Plazebo zu einer statistisch signifikanten Lebensverlängerung bei Patienten mit einem hormonrefraktären Prostatakarzinom kommt. Das Nebenwirkungsprofil der Vakzinetherapie ist dabei als äußerst günstig zu bezeichnen. Derzeit befinden sich Studien in Planung, die sowohl auf eine Kombination mit anderen Substanzen als auch auf die Behandlung früherer Krankheitsstadien abzielen.

Abstract

Vaccine therapy of prostate cancer has been increasingly studied in trials over the past few years. The different vaccine techniques are quite variable and are predominantly used in patients with advanced hormone-refractory prostate cancer. In this review, vaccine techniques using tumor cells, dendritic cells or poxvirus are analyzed. For theses approaches phase-III trials are being planned, have been initiated or are already completed. Many trials demonstrate the efficacy with regard to endpoints such as stimulation of the immune system and/or biochemical response and/or clinical response. Recently, one vaccine approach using autologous dendritic cells demonstrated a statistically significant prolongation of overall survival compared to placebo in patients with hormone-refractory prostate cancer. Side effects of vaccination are generally mild. At present, there are trials are being planned or are already ongoing that combine vaccine with other treatment strategies or enroll patients with earlier disease stages.

Schlüsselwörter

Prostatakarzinom - Immuntherapie - Vakzine - Tumorzelle - dendritische Zelle - Virus - Antigen - Zytokin - Wachstumsfaktor.

Key words

Prostate cancer - immunotherapy - vaccine - tumor cell - dendritic cell - virus - antigen - cytokine - growth factor.

Literatur

  • 1 www.rki.de (aufgerufen am 30. Juli 2005). 
    Google Scholar
  • 2 Jemal A, Murray T, Ward E, Samuels A, Tiwari R C, Ghafoor A, Feuer E J, Thun M J. Cancer statistics, 2005.  CA Cancer J Clin. 2005;  26 10-30
    PubMedGoogle Scholar
  • 3 Small E J, Schellhammer P F, Higano C S, Neumanaitis J, Valone F, Hershberg R. Results of a Placebo-Controlled Phase III Trial of Immunotherapy with APC8015 for Patients with Hormone Refractory Prostate Cancer (HRPC).  J Clin Oncol. 2005;  26 378 s (Abs 4500)
    PubMedGoogle Scholar
  • 4 www.auanet.org (aufgerufen am 30. Juli 2005). 
    Google Scholar
  • 5 www.asco.org (aufgerufen am 30. Juli 2005). 
    Google Scholar
  • 6 www.uroweb.net (aufgerufen am 30. Juli 2005). 
    Google Scholar
  • 7 www.dgu.de (aufgerufen am 30. Juli 2005). 
    Google Scholar
  • 8 Ragde H, Cavanagh W A, Tjoa B A. Dendritic cell based vaccines: progress in immunotherapy studies for prostate cancer.  J Urol. 2004;  26 2532-2538
    PubMedGoogle Scholar
  • 9 Swindle P W, Tepes S, Clements J. DC therapy for prostate cancer.  Cytotherapy. 2004;  26 164-171
    PubMedGoogle Scholar
  • 10 www.clinicaltrials.gov (aufgerufen am 30. Juli 2005). 
    Google Scholar
  • 11 Ward S, Casey D, Labarthe M C, Whelan M, Galgleish A, Pandha H, Todryk S. Immunotherapeutic potential of whole tumor cells.  Cancer Immunol Immunother. 2002;  26 351-357
    PubMedGoogle Scholar
  • 12 Simons J W, Mikhak B, Chang J F, DeMarzo A M, Carducci M A, Lim M, Weber C E, Baccala A A, Goemann M A, Clift S M, Ando D G, Levitsky H I, Cohen L K, Sanda M G, Mulligan R C, Partin A W, Carter H B, Piantadosi S, Marshall F F, Nelson W G. Induction of immunity to prostate cancer antigens: results of a clinical trial of vaccination with irradiated autologous prostate tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor using ex vivo gene transfer.  Cancer Res. 1999;  26 5160-5168
    PubMedGoogle Scholar
  • 13 Simons J W, Small E, Nelson W, Nemunaitis J, Centeno A, Dula E, Urba W, Smith D, Marshall F, Borellini F, Sy J, Marshall M. Phase II trials of a GM-CSF gene-transduced prostate cancer cell line vaccine (GVAX) demonstrate anti-tumor activity.  Proc Am Soc Clin Oncol. 2001;  26 269 a (Abs 1073)
    PubMedGoogle Scholar
  • 14 Simons J, Nelson W, Nemunaitis J, Centeno A, Dula E, Urba W, Smith D, Marshall F, Howard C, Ando D, Small E. Phase II trials of a GM-CSF gene-transduced prostate cancer cell line vaccine (GVAX) in hormone refractory prostate cancer.  Proc Am Soc Clin Oncol. 2002;  26 183 a (Abs 729)
    PubMedGoogle Scholar
  • 15 Simons J, Higano C, Corman J, Hudes G, Centeno A, Dula E, Smith D, Steidle C, Sacks N, Small E. A phase I/II study of high dose allogeneic GM-CSF gene-transduced prostate cancer cell line vaccine in patients with metastatic hormone-refractory prostate cancer.  Proc Am Soc Clin Oncol. 2003;  26 166 (Abs 667)
    PubMedGoogle Scholar
  • 16 Small E, Higano C, Smith D, Corman J, Centeno A, Steidle C, Gittelman M, Hudes G, Sacks N, Simons J. A phase 2 study of an allogeneic GM-CSF gene-transduced prostate cancer cell line vaccine in patients with metastatic hormone-refractory prostate cancer (HRPC).  Proc Am Soc Clin Oncol. 2004;  26 396 (Abs 4565)
    PubMedGoogle Scholar
  • 17 Simons J W, Higano C, Smith D, Corman J, Steidle C, Gittelman M, Hudes G, Aimi J, Sacks N, Small E. Clinical and immunologic findings in a phase 2 study of a GM-CSF-secreting prostate cancer cell line vaccine in patients with metastatic hormone-refractory prostate cancer (met HPRC).  J Clin Oncol. 2005;  26 170 s (Abs 2517)
    PubMedGoogle Scholar
  • 18 www.cellgenesys.com (aufgerufen am 30. Juli 2005). 
    Google Scholar
  • 19 Michael A, Ball G, Quatan N, Wushishi F, Russell N, Whelan J, Chakraborty P, Leader D, Whelan M, Pandha H. Delayed disease progression after allogeneic cell vaccination in hormone-resistant prostate cancer and correlation with immunologic variables.  Clin Cancer Res. 2005;  26 4469-4478
    PubMedGoogle Scholar
  • 20 Horoszewicz J S, Leong S S, Chu T M, Wajsman Z L, Friedman M, Papsidero L, Kim U, Chai L S, Kakati S, Arya S K, Sandberg A A. The LNCaP cell line - a new model for studies on human prostatic carcinoma.  Prog Clin Biol Res. 1980;  26 115-112
    PubMedGoogle Scholar
  • 21 van Steenbrugge G J, Groen M, van Dongen J W, Bolt J, van der Korput H, Trapman J, Hasenson M, Horoszewicz J. The human prostatic carcinoma cell line LNCaP and its derivatives. An overview.  Urol Res. 1989;  26 71-77
    PubMedGoogle Scholar
  • 22 Lang S H, Stower M, Maitland N J. In vitro modelling of epithelial and stromal interactions in non-malignant and malignant prostates.  Br J Cancer. 2000;  26 990-997
    PubMedGoogle Scholar
  • 23 Maitland N J, Macintosh C A, Hall J, Sharrard M, Quinn G, Lang S. In vitro models to study cellular differentiation and function in human prostate cancers.  Radiat Res. 2001;  26 133-142
    PubMedGoogle Scholar
  • 24 Dawson L A, Maitland N J, Turner A J, Usmani B A. Stromal-epithelial interactions influence prostate cancer cell invasion by altering the balance of metallopeptidase expression.  Br J Cancer. 2004;  26 1577-1582
    PubMedGoogle Scholar
  • 25 Sobel R E, Sadar M D. Cell lines used in prostate cancer research: a compendium of old and new lines-part 2.  J Urol. 2005;  26 360-372
    PubMedGoogle Scholar
  • 26 Eaton J D, Perry M J, Nicolson S, Guckian M, Russel N, Whelan M, Kirby R S. Allogeneic whole-cell vaccine: a phase I/II study in men with hormone-refractory prostate cancer.  BJU Int. 2002;  26 19-26
    PubMedGoogle Scholar
  • 27 Michael A, Quatan N, Whelan M, Kendall A, Pandha H. Preliminary results of a phase I/II study to determine the safety, tolerability and efficacy of the allogeneic whole cell vaccine in patients with hormone refractory prostate cancer.  Proc Am Soc Clin Oncol. 2003;  26 188 (Abs 752)
    PubMedGoogle Scholar
  • 28 Michael A, Quatan N, Russel N, Wushishi F, Whelan J, Whelan M, Pandha H. Allogenic whole cell vaccination significantly delays disease progression in hormone-relapsed prostrate cancer: final data from a phase II study.  Eur J Cancer. 2004;  26 8 (Abs 260)
    PubMedGoogle Scholar
  • 29 Pandha H S, Michael A, Quatan N, Wushishi F, Russell N, Whelan J, Whelan M. The effect of whole cell allogeneic vaccination on the progression of hormone-relapsed prostate cancer.  Proc Am Soc. 2004;  26 438 (Abs 4735)-438 (Abs 4735
    PubMedGoogle Scholar
  • 30 Dalgleish A G, Quatan N, Michael A. , Wushishi F, Pandha H. Increased time to progression and sustained PSA velocity responses in a Phase II trial in advanced metastatic prostate cancer following treatment with ONY-P1, an allogeneic whole cell vaccine.  J Clin Oncol. 2005;  26 434 s (Abs 4726)
    PubMedGoogle Scholar
  • 31 www.onyvax.com (aufgerufen am 30. Juli 2005). 
    Google Scholar
  • 32 Ridgway D. The first 1000 dendritic cell vaccinees.  Cancer Invest. 2003;  26 873-886
    PubMedGoogle Scholar
  • 33 Murphy G, Tjoa B, Ragde H, Kenny G, Boynton A. Phase I clinical trial: T-cell therapy for prostate cancer using autologous dendritic cells pulsed with HLA-A0201-specific peptides from prostate-specific membrane antigen.  Prostate. 1996;  26 371-380
    PubMedGoogle Scholar
  • 34 Murphy G P, Tjoa B A, Simmons S J, Ragde H, Rogers M, Elgamal A, Kenny G M, Troychak M J, Salgaller M L, Boynton A L. Phase II prostate cancer vaccine trial: report of a study involving 37 patients with disease recurrence following primary treatment.  Prostate. 1999 a ;  26 54-59
    PubMedGoogle Scholar
  • 35 Murphy G P, Tjoa B A, Simmons S J, Jarisch J, Bowes V A, Ragde H, Rogers M, Elgamal A, Kenny G M, Cobb O E, Ireton R C, Troychak M J, Salgaller M L, Boynton A L. Infusion of dendritic cells pulsed with HLA-A2-specific prostate-specific membrane antigen peptides: a phase II prostate cancer vaccine trial involving patients with hormone-refractory metastatic disease.  Prostate. 1999 b ;  26 73-78
    PubMedGoogle Scholar
  • 36 www.nwbio.com (aufgerufen am 30. Juli 2005). 
    Google Scholar
  • 37 Knutson K L. Technology evaluation: DCVax, Northwest Biotherapeutics.  Curr Opin Mol Ther. 2002;  26 403-407
    PubMedGoogle Scholar
  • 38 Freeman L M, Krynyckyi B R, Li Y, Korupulu G, Saleemi K, Haseman M K, Kahn D,. The role of (111) In Capromab Pendetide (Prosta-ScintR) immunoscintigraphy in the management of prostate cancer.  Q J Nucl Med. 2002;  26 131-137
    PubMedGoogle Scholar
  • 39 Small E J, Fratesi P, Reese D M, Strang G, Laus R, Peshwa M V, Valone F H. Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells.  J Clin Oncol. 2000;  26 3894-3903
    PubMedGoogle Scholar
  • 40 Schellhammer P F, Hershberg R M. Immunotherapy with autologous antigen presenting cells for the treatment of androgen independent prostate cancer.  World J Urol. 2005;  26 47-49
    PubMedGoogle Scholar
  • 41 Beinart G, Rini B I, Weinberg V, Small E J. Antigen-presenting cells 8015 (provenge) in patients with androgen-dependent, biochemically relapsed prostate cancer.  Clin Prostate Cancer. 2005;  26 55-60
    PubMedGoogle Scholar
  • 42 Burch P A, Croghan G A, Gastineau D A, Jones L A, Kaur J S, Kylstra J W, Richardson R L, Valone F H, Vuk-Pavlovic S. Immunotherapy (APC8015, Provenge) targeting prostatic acid phosphatase can induce durable remission of metastatic androgen-independent prostate cancer: a Phase 2 trial.  Prostate. 2004;  26 197-204
    PubMedGoogle Scholar
  • 43 www.dendreon.com (aufgerufen am 30. Juli 2005). 
    Google Scholar
  • 44 Doehn C, Jocham D. Technology evaluation: TG-1031, Transgene SA.  Curr Opin Mol Ther. 2000;  26 106-111
    PubMedGoogle Scholar
  • 45 www.transgene.fr (aufgerufen am 30. Juli 2005). 
    Google Scholar
  • 46 Eder J P, Kantoff P W, Bubley G J, Conner L A. A phase I trial of recombinant vaccinia virus, PROSTVAC, that expresses prosatet specific antigen as a vaccine in men with advanced prostate cancer.  Proc Am Soc Clin Oncol. 1998;  34 (Abs 1672)
    PubMedGoogle Scholar
  • 47 Gulley J L, Dahut W, Chen A, Arlen P, Bastain A, Tsang K, Schlom J, Panicali D, Hamilton M. A phase I study of a vaccine using recombinant vaccinia virus expressing PSA (rV-PSA) in patients with androgen independent prostate cancer (AIPC).  Proc Am Soc Clin Oncol. 2001;  26 273 a (Abs 1088)
    PubMedGoogle Scholar
  • 48 Doehn C, Jocham D. Technology evaluation: PROSTVAC, Therion.  Curr Opin Mol Ther. 2002;  26 528-534
    PubMedGoogle Scholar
  • 49 Eder J P, Kantoff P W, Roper K, GuangXian X, Oh W K, Bubley G J, Kaufman D, Panacali D, Tsang A, Schlom J, Kufe D W. A phase I trial of recombinant prosatet specific antigen expressing vaccinia virus vaccine, PROSTVAC (rv-PSA), in avanced prostate cancer.  Proc Am Soc Clin Oncol. 1999;  18 (Abs 1692)
    PubMedGoogle Scholar
  • 50 Gulley J, Chen A P, Dahut W, Arlen P M, Bastian A, Steinberg S M, Tsang K, Panicali D, Poole D, Schlom J, Michael Hamilton J. Phase I study of a vaccine using recombinant vaccinia virus expressing PSA (rV-PSA) in patients with metastatic androgen-independent prostate cancer.  Prostate. 2002;  26 109-117
    PubMedGoogle Scholar
  • 51 Arlen P A, Gulley J, Novik L, Hamilton J M, Bastian A, Pannicali D, Palena C, Tsang K Y, Schlom J, Dahut W L. A randomized phase II trial of either vaccine therapy (recombinant pox viruses expressing PSA and the B7.1 costimulatory molecule) versus hormone therapy (nilutamide) in patients (pts) with hormone refractory prostate cancer and no radiographic evidence of disease.  Proc Am Soc Clin Oncol. 2002;  26 183 a (Abs 728)
    PubMedGoogle Scholar
  • 52 Kaufmann H L, Wang W, Manola J, DiPaola R S, Ko Y J, Sweeney C, Whiteside T L, Schlom J, Wilding G, Weiner L M. Phase II randomized study of vaccine treatment of advanced prostate cancer (E7897): a trial of the Eastern Cooperative Oncology Group.  J Clin Oncol. 2004;  26 2122-2132
    PubMedGoogle Scholar
  • 53 Arlen P M, Gulley J, Dahut W, Skarupa L, Morin S, Pazdur M, Todd N, Panicali D, Tsang K Y, Schlom J. A phase I study of sequential vaccinations with recombinant Fowlpox-PSA (L155)-TRICOM (rF)alone, or in combination with recombinant vaccinia-PSA (L155)-TRICOM (rV), and the role of GM-CSF, in patients (Pts) with prostate cancer.  Proc Am Soc Clin Oncol. 2004;  26 168 (Abs 2522)
    PubMedGoogle Scholar

Dr. med. Christian Doehn

Ltd. Oberarzt der Klinik und Poliklinik für Urologie · Universitätsklinikum Schleswig-Holstein (UKSH) · Campus Lübeck

Ratzeburger Allee 160

23538 Lübeck

Phone: +49/451/5 00-61 13

Fax: +49/451/5 00-46 66

Email: doehn@medinf.mu-luebeck.de

      >