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Cancer Immunol Immunother. 2016 Mar;65(3):327-39. doi: 10.1007/s00262-016-1796-7. Epub 2016 Feb 10.

Prophylactic vaccines are potent activators of monocyte-derived dendritic cells and drive effective anti-tumor responses in melanoma patients at the cost of toxicity.

Author information

1
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
2
Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, The Netherlands.
3
Department of Radiology and Nuclear Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands.
4
Department of Hematology, Radboud University Medical Centre, Nijmegen, The Netherlands.
5
Department of Pathology, Radboud University Medical Centre, Nijmegen, The Netherlands.
6
Department of Dermatology, Radboud University Medical Centre, Nijmegen, The Netherlands.
7
Department of Pulmonary Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands.
8
Department of Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands.
9
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. Gerty.Schreibelt@radboudumc.nl.

Abstract

Dendritic cell (DC)-based immunotherapy is explored worldwide in cancer patients, predominantly with DC matured with pro-inflammatory cytokines and prostaglandin E2. We studied the safety and efficacy of vaccination with monocyte-derived DC matured with a cocktail of prophylactic vaccines that contain clinical-grade Toll-like receptor ligands (BCG, Typhim, Act-HIB) and prostaglandin E2 (VAC-DC). Stage III and IV melanoma patients were vaccinated via intranodal injection (12 patients) or combined intradermal/intravenous injection (16 patients) with VAC-DC loaded with keyhole limpet hemocyanin (KLH) and mRNA encoding tumor antigens gp100 and tyrosinase. Tumor antigen-specific T cell responses were monitored in blood and skin-test infiltrating-lymphocyte cultures. Almost all patients mounted prophylactic vaccine- or KLH-specific immune responses. Both after intranodal injection and after intradermal/intravenous injection, tumor antigen-specific immune responses were detected, which coincide with longer overall survival in stage IV melanoma patients. VAC-DC induce local and systemic CTC grade 2 and 3 toxicity, which is most likely caused by BCG in the maturation cocktail. The side effects were self-limiting or resolved upon a short period of systemic steroid therapy. We conclude that VAC-DC can induce functional tumor-specific responses. Unfortunately, toxicity observed after vaccination precludes the general application of VAC-DC, since in DC maturated with prophylactic vaccines BCG appears to be essential in the maturation cocktail.

KEYWORDS:

Dendritic cells; Immunotherapy; Maturation; Melanoma; Prophylactic vaccines; Toll-like receptor ligands

PMID:
26861670
PMCID:
PMC4779136
DOI:
10.1007/s00262-016-1796-7
[Indexed for MEDLINE]
Free PMC Article

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