Autologous monocyte-derived DC vaccination combined with cisplatin in stage III and IV melanoma patients: a prospective, randomized phase 2 trial

Steve Boudewijns, Martine Bloemendal, Nienke de Haas, Harm Westdorp, Kalijn F. Bol, Gerty Schreibelt, Erik H.J.G. Aarntzen, W. Joost Lesterhuis, Mark A.J. Gorris, Alexandra Croockewit, Lieke L. van der Woude, Michelle M. van Rossum, Marieke Welzen, Anna de Goede, Stanleyson V. Hato, Winette T.A. van der Graaf, Cornelis J.A. Punt, Rutger H.T. Koornstra, Winald R. Gerritsen, Carl G. FigdorI. Jolanda M. de Vries

Research output: Contribution to journalArticle

Abstract

Background: Autologous dendritic cell (DC) vaccines can induce tumor-specific T cells, but their effect can be counteracted by immunosuppressive mechanisms. Cisplatin has shown immunomodulatory effects in vivo which may enhance efficacy of DC vaccination. Methods: This is a prospective, randomized, open-label phase 2 study (NCT02285413) including stage III and IV melanoma patients receiving 3 biweekly vaccinations of gp100 and tyrosinase mRNA-loaded monocyte-derived DCs with or without cisplatin. Primary objectives were to study immunogenicity and feasibility, and secondary objectives were to assess toxicity and survival. Results: Twenty-two stage III and 32 stage IV melanoma patients were analyzed. Antigen-specific CD8+ T cells were found in 44% versus 67% and functional T cell responses in 28% versus 19% of skin-test infiltrating lymphocytes in patients receiving DC vaccination with and without cisplatin, respectively. Four patients stopped cisplatin because of toxicity and continued DC monotherapy. No therapy-related grade 3 or 4 adverse events occurred due to DC monotherapy. During combination therapy, one therapy-related grade 3 adverse event, decompensated heart failure due to fluid overload, occurred. The clinical outcome parameters did not clearly suggest significant differences. Conclusions: Combination of DC vaccination and cisplatin in melanoma patients is feasible and safe, but does not seem to result in more tumor-specific T cell responses or improved clinical outcome, when compared to DC vaccination monotherapy.

Original languageEnglish
Pages (from-to)477-488
Number of pages12
JournalCancer immunology, immunotherapy
Volume69
Issue number3
DOIs
Publication statusPublished - 1 Mar 2020

Fingerprint Dive into the research topics of 'Autologous monocyte-derived DC vaccination combined with cisplatin in stage III and IV melanoma patients: a prospective, randomized phase 2 trial'. Together they form a unique fingerprint.

  • Cite this

    Boudewijns, S., Bloemendal, M., de Haas, N., Westdorp, H., Bol, K. F., Schreibelt, G., Aarntzen, E. H. J. G., Lesterhuis, W. J., Gorris, M. A. J., Croockewit, A., van der Woude, L. L., van Rossum, M. M., Welzen, M., de Goede, A., Hato, S. V., van der Graaf, W. T. A., Punt, C. J. A., Koornstra, R. H. T., Gerritsen, W. R., ... de Vries, I. J. M. (2020). Autologous monocyte-derived DC vaccination combined with cisplatin in stage III and IV melanoma patients: a prospective, randomized phase 2 trial. Cancer immunology, immunotherapy, 69(3), 477-488. https://doi.org/10.1007/s00262-019-02466-x