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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 3/2020

Open Access 01-03-2020 | Melanoma | Clinical Trial Report

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

Authors: 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. Figdor, I. Jolanda M. de Vries

Published in: Cancer Immunology, Immunotherapy | Issue 3/2020

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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.
Appendix
Available only for authorised users
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Metadata
Title
Autologous monocyte-derived DC vaccination combined with cisplatin in stage III and IV melanoma patients: a prospective, randomized phase 2 trial
Authors
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. Figdor
I. Jolanda M. de Vries
Publication date
01-03-2020
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 3/2020
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-019-02466-x

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