Original Article

Cancer Immunology, Immunotherapy

, Volume 60, Issue 2, pp 261-271

First online:

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 OudardAffiliated withMedical Oncology Department, Georges Pompidou European HospitalAP-HP, Université Paris DescartesINSERM U970 PARCC Email author 
  • , Olivier RixeAffiliated withExperimental Therapeutics Program, Division of Hematology/Oncology, University of Cincinnati Cancer Institute
  • , Benoit BeuselinckAffiliated withMedical Oncology Department, Georges Pompidou European HospitalAP-HP, Université Paris Descartes
  • , Claude LinassierAffiliated withBretonneau Hospital
  • , Eugeniu BanuAffiliated withMedical Oncology Department, Georges Pompidou European HospitalAP-HP, Université Paris Descartes
  • , Jean-Pascal MachielsAffiliated withCliniques Universitaires Saint-Luc
  • , Marion BaudardAffiliated withLapeyronie Hospital
  • , François RingeisenAffiliated withMichallon Hospital
  • , Thierry VeluAffiliated withErasme Hospital
    • , Marie-Aude Lefrere-BeldaAffiliated withMedical Oncology Department, Georges Pompidou European HospitalAP-HP, Université Paris Descartes
    • , Jean-Marc LimacherAffiliated withTransgene S.A.
    • , W. H. FridmanAffiliated withMedical Oncology Department, Georges Pompidou European HospitalAP-HP, Université Paris Descartes
    • , Michel AziziAffiliated withCentre d’Investigation Clinique, Georges Pompidou European Hospital
    • , Bruce AcresAffiliated withTransgene S.A.
    • , Eric TartourAffiliated withMedical Oncology Department, Georges Pompidou European HospitalAP-HP, Université Paris DescartesINSERM U970 PARCC

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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