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

Author:

Boudewijns SteveORCID,Bloemendal MartineORCID,de Haas NienkeORCID,Westdorp HarmORCID,Bol Kalijn F.ORCID,Schreibelt GertyORCID,Aarntzen Erik H. J. G.ORCID,Lesterhuis W. JoostORCID,Gorris Mark A. J.ORCID,Croockewit Alexandra,van der Woude Lieke L.,van Rossum Michelle M.,Welzen Marieke,de Goede Anna,Hato Stanleyson V.,van der Graaf Winette T. A.,Punt Cornelis J. A.ORCID,Koornstra Rutger H. T.ORCID,Gerritsen Winald R.ORCID,Figdor Carl G.ORCID,de Vries I. Jolanda M.ORCID

Abstract

AbstractBackgroundAutologous 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.MethodsThis 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.ResultsTwenty-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.ConclusionsCombination 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.

Funder

Dutch Cancer Society

Netherlands Organisation for Scientific Research

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Oncology,Immunology,Immunology and Allergy

Reference39 articles.

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2. Bloemendal M (2019) Novel strategies in dendritic-cell based immunotherapy—focusing on adjuvant treatment of stage III melanoma, departments of Tumor Immunology and Medical Oncology. Radboud University Medical Center, Nijmegen

3. Palucka K, Banchereau J (2013) Dendritic-cell-based therapeutic cancer vaccines. Immunity 39(1):38–48

4. Boudewijns S et al (2016) Adjuvant dendritic cell vaccination induces tumor-specific immune responses in the majority of stage III melanoma patients. Oncoimmunology 5(7):e1191732

5. Aarntzen EH et al (2012) Vaccination with mRNA-electroporated dendritic cells induces robust tumor antigen-specific CD4+ and CD8+ T cells responses in stage III and IV melanoma patients. Clin Cancer Res 18(19):5460–5470

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