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Allogeneic gene-modified tumor cells (RCC-26/IL-7/CD80) as a vaccine in patients with metastatic renal cell cancer: a clinical phase-I study

Gene Therapy volume 18, pages 354–363 (2011)Cite this article

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Abstract

Despite novel targeted agents, prognosis of metastatic renal cell cancer (RCC) remains poor, and experimental therapeutic strategies are warranted. Transfection of tumor cells with co-stimulatory molecules and/or cytokines is able to increase immunogenicity. Therefore, in our clinical study, 10 human leukocyte antigen (HLA)-A*0201+ patients with histologically-confirmed progressive metastatic clear cell RCC were immunized repetitively over 22 weeks with 2.5–40 × 106 interleukin (IL)-7/CD80 cotransfected allogeneic HLA-A*0201+ tumor cells (RCC26/IL-7/CD80). Endpoints of the study were feasibility, safety, immunological and clinical responses. Vaccination was feasible and safe. In all, 50% of the patients showed stable disease throughout the study; the median time to progression was 18 weeks. However, vaccination with allogeneic RCC26/IL-7/CD80 tumor cells was not able to induce TH1-polarized immune responses. A TH2 cytokine profile with increasing amounts of antigen-specific IL-10 secretion was observed in most of the responding patients. Interferon-γ secretion by patient lymphocytes upon antigen-specific and non-specific stimulation was substantially impaired, both before and during vaccination, as compared with healthy controls. This is possibly due to profound tumor-induced immunosuppression, which may prevent induction of antitumor immune responses by the gene-modified vaccine. Vaccination in minimal residual disease with concurrent depletion of regulatory cells might be one strategy to overcome this limitation.

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Acknowledgements

This work was supported by grants from the Federal Ministry of Education and Research (01 GE 9624/1) to TB and DJS, German Research Foundation (SFB-455, SFB-650) and Helmholtz-Association for Immunotherapy of Cancer.

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Authors and Affiliations

  1. Department of Hematology, Oncology and Tumor Immunology, Charité-University Medicine Berlin, Campus Virchow-Klinikum and Campus Berlin-Buch, Berlin, Germany

    J Westermann, A Flörcken, A van Lessen, J Kopp, A Takvorian, B Dörken & A Pezzutto

  2. Institute of Immunology, Charité-University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany

    G Willimsky & T Blankenstein

  3. Max Delbrück Center for Molecular Medicine, Berlin, Germany

    J Westermann, G Willimsky, B Dörken, T Blankenstein & A Pezzutto

  4. Department of Pathology, Charité-University Medicine Berlin, Campus Charité Mitte, Berlin, Germany

    K Jöhrens

  5. Department of Dermatology, Charité-University Medicine Berlin, Campus Charité Mitte, Berlin, Germany

    A Lukowsky

  6. Department of Transfusion Medicine, Campus Charité-University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany

    C Schönemann

  7. Institute of Immunology, Charité-University Medicine Berlin, Campus Charité Mitte, Berlin, Germany

    B Sawitzki

  8. Laboratory of Tumor Immunology, LIFE Center, Ludwig-Maximilians-University, Munich, Germany

    H Pohla

  9. Institute of Molecular Immunology, Helmholtz Zentrum München, German Research Center for Environmental Health, and Clinical Cooperation Group ‘Immune Monitoring’, Munich, Germany

    H Pohla & D J Schendel

  10. Department of Chemical Biology, Helmholtz Center for Infection Research, Braunschweig, Germany

    R Frank

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Westermann, J., Flörcken, A., Willimsky, G. et al. Allogeneic gene-modified tumor cells (RCC-26/IL-7/CD80) as a vaccine in patients with metastatic renal cell cancer: a clinical phase-I study. Gene Ther 18, 354–363 (2011). https://doi.org/10.1038/gt.2010.143

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