Cancer Immunology, Immunotherapy

, Volume 60, Issue 2, pp 261–271

A phase II study of the cancer vaccine TG4010 alone and in combination with cytokines in patients with metastatic renal clear-cell carcinoma: clinical and immunological findings

  • Stéphane Oudard
  • Olivier Rixe
  • Benoit Beuselinck
  • Claude Linassier
  • Eugeniu Banu
  • Jean-Pascal Machiels
  • Marion Baudard
  • François Ringeisen
  • Thierry Velu
  • Marie-Aude Lefrere-Belda
  • Jean-Marc Limacher
  • W. H. Fridman
  • Michel Azizi
  • Bruce Acres
  • Eric Tartour
Original Article

Abstract

MUC1 over-expression in renal clear-cell carcinoma (RCC) is associated with poor prognosis. This phase II study determined the efficacy and tolerability of TG4010, a cancer vaccine based on a modified vaccinia virus expressing MUC1 and interleukin-2, in combination with cytokines, as first-line therapy in metastatic RCC. Thirty-seven patients with progressive, MUC1-positive RCC received TG4010 108 pfu/inj weekly for 6 weeks, then every 3 weeks until progression, when TG4010 was continued in combination with interferon-α2a and interleukin-2. Assessments included clinical response (primary endpoint), safety, time to treatment failure (TTF), overall survival (OS), and immune response. No objective clinical responses occurred. Five of the 27 evaluable patients (18%) had stable disease for >6 months with TG4010 alone and six of 20 patients (30%) had stable disease for >6 months with TG4010 plus cytokines. Median TTF was 4.1, 3.6, and 9.3 months for monotherapy, combination therapy, and overall, respectively. Median OS was 19.3 months for all patients and 22.4 months combination therapy recipients. The most frequent TG4010-related adverse events were minor-to-moderate injection-site reactions, fatigue, and flu-like symptoms. Six of 28 patients showed a MUC1 CD4+ T cell proliferative response during therapy. Anti-MUC1 CD8+ T cells were detected before and after therapy in 3 and 4 patients, respectively. MUC1-specific CD8+ T cell responses were associated with longer survival. Therapy with TG4010 plus cytokines appears to be feasible and well tolerated in patients with metastatic RCC. However, these data should be interpreted with caution, as additional prospective studies are necessary to clarify the clinical efficacy of this therapy.

Keywords

Renal cell carcinoma Vaccine TG4010 Immune response MUC1 Cytokines 

Supplementary material

262_2010_935_MOESM1_ESM.pdf (182 kb)
Supplementary material 1 (PDF 181 kb)

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Stéphane Oudard
    • 1
    • 2
    • 3
  • Olivier Rixe
    • 4
  • Benoit Beuselinck
    • 1
    • 2
  • Claude Linassier
    • 5
  • Eugeniu Banu
    • 1
    • 2
  • Jean-Pascal Machiels
    • 6
  • Marion Baudard
    • 7
  • François Ringeisen
    • 8
  • Thierry Velu
    • 9
  • Marie-Aude Lefrere-Belda
    • 1
    • 2
  • Jean-Marc Limacher
    • 10
  • W. H. Fridman
    • 1
    • 2
  • Michel Azizi
    • 11
  • Bruce Acres
    • 10
  • Eric Tartour
    • 1
    • 2
    • 3
  1. 1.Medical Oncology DepartmentGeorges Pompidou European HospitalParis Cedex 15France
  2. 2.AP-HPUniversité Paris DescartesParisFrance
  3. 3.INSERM U970 PARCCParisFrance
  4. 4.Experimental Therapeutics Program, Division of Hematology/OncologyUniversity of Cincinnati Cancer InstituteCincinnatiUSA
  5. 5.Bretonneau HospitalToursFrance
  6. 6.Cliniques Universitaires Saint-LucBrusselsBelgium
  7. 7.Lapeyronie HospitalMontpellierFrance
  8. 8.Michallon HospitalGrenobleFrance
  9. 9.Erasme HospitalBrusselsBelgium
  10. 10.Transgene S.A.StrasbourgFrance
  11. 11.Centre d’Investigation CliniqueGeorges Pompidou European HospitalParisFrance

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