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Review
. 2008 Oct;57(10):1559-68.
doi: 10.1007/s00262-008-0553-y. Epub 2008 Jul 10.

Dendritic cell vaccination and immune monitoring

E H J G Aarntzen  1 , C G Figdor, G J Adema, C J A Punt, I J M de Vries
Affiliations
Review

Dendritic cell vaccination and immune monitoring

E H J G Aarntzen et al. Cancer Immunol Immunother. 2008 Oct.

Abstract

We exploited dendritic cells (DC) to vaccinate melanoma patients. We recently demonstrated a statistical significant correlation between favorable clinical outcome and the presence of vaccine-related tumor antigen-specific T cells in delayed type hypersensitivity (DTH) skin biopsies. However, favorable clinical outcome is only observed in a minority of the treated patients. Therefore, it is obvious that current DC-based protocols need to be improved. For this reason, we study in small proof of principle trials the fate, interactions and effectiveness of the injected DC.

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Figures

Fig. 1
Fig. 1
Monitoring the accuracy of delivery of SPIO-labeled cells using MR imaging and scintigraphy. Monocytes are obtained by cytopheresis from stage III melanoma patients (a), they are cultured and labeled with SPIO particles and 111Indium (b). The cells are then injected intranodally into the lymph node basin that is to be resected and their biodistribution is monitored in vivo by scintigraphy (c) and MRI (d). The lymph node basin is resected (e) and separate lymph nodes are visualized with high-resolution MRI at 7 Tesla (f) and histology (g)
Fig. 2
Fig. 2
Specificity in DTH-infiltrated leukocyte (DIL) cultures derived from patients vaccinated with peptide-loaded DC. a In DIL cultured from a DTH performed with DC loaded with gp100 and KLH only T cells positive for the gp100 tetramers were observed. Tyrosinase tetramer-positive cells were observed in the DIL derived from a DTH induced with tyrosinase peptide-loaded DC. The production of IFNγ corresponded with the observed tetramer positivity. b DIL derived from a DTH site induced by DC loaded with gp100 and KLH did not produce cytokines in response to the HLA-A2.1-positive melanoma cell line BLM transfected with control antigen G250 (a) whereas BLM transfected with gp100 was recognized (b). The DIL culture also recognized an HLA-A2.1-positive melanoma cell line expressing both gp100 and tyrosinase (c)
Fig. 3
Fig. 3
Presence of tetramer-specific T cells highly correlates with progression free survival in melanoma patients. Correlation between the presence of specific T cells and clinical outcome is shown in this plot comparing the progression free survival of stage IV melanoma patients with (closed line) and without (hatched line) tumor-specific T cells in their DTH-infiltrated lymphocytes
See this image and copyright information in PMC

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