Publication in Cancer Research

Tel en Aarntzen

In the latest issue of Cancer Research, Erik Aarntzen (Dept. of Medical Oncology) and Jurjen Tel (Dept. of Tumor Immunology) together with a joint team of physicians and researchers, involving the Departments of Tumor Immunology, Medical Oncology, Hematology, Nuclear Medicine and Dermatology, published their findings entitled "Natural human pDCs induce antigen specific T cell responses and enhance overall survival in melanoma patients".

During the past decade, early clinical trials carried out by investigators throughout the world have shown that vaccination with dendritic cells (DCs) loaded with tumor-peptides can induce tumor-specific immune responses in advanced cancer patients. However, the clinical results have been somewhat disappointing, as only a minority of the treated patients show long-lasting clinical responses. Thus far, virtually all clinical trials were based on ex vivo generated DCs, either derived from monocytes or CD34+ progenitor-cells. We hypothesized that extensive culturing and/ or manipulation might have limited their immunogenic potential. This prompted us to explore the possibility of exploiting scarce naturally circulating DCs such as plasmacytoid DCs. In this worlds' first phase I clinical study we demonstrate the feasibility and the efficacy of this approach as demonstrated by a significant extended survival of late stage melanoma patients. This study, which we initiated 4 years ago included 15 patients that received activated plasmacytoid DCs. No less than 7 out of the 15 patients vaccinated were still alive even two years after treatment. This observation is remarkable, because the mean survival of these late stage melanoma patients is generally 22 months. Together, we believe that the use of activated natural pDCs mark a new era in the development of DC-based vaccines and are potentially much stronger in inducing immune responses when compared to ex vivo generated DCs that have been used thus far.

Tel J, Aarntzen EH, Baba T, Schreibelt G, Schulte BM, Benitez-Ribas D, Boerman OC, Croockewit S, Oyen WJ, van Rossum M, Winkels G, Coulie PG, Punt CJ, Figdor CG, de Vries IJ, Natural human plasmacytoid dendritic cells induce antigen-specific T-cell responses in melanoma patients. Cancer Res. 2013 Feb 1;73(3):1063-75.

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