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01-12-2006 | Original Article

In vitro priming of tumor-specific cytotoxic T lymphocytes using allogeneic dendritic cells derived from the human MUTZ-3 cell line

Authors: Saskia J. A. M. Santegoets, Marco W. J. Schreurs, Allan J. Masterson, Ying Poi Liu, Steffen Goletz, Hans Baumeister, Esther W. M. Kueter, Sinéad M. Lougheed, Alfons J. M. van den Eertwegh, Rik J. Scheper, Erik Hooijberg, Tanja D. de Gruijl

Published in: Cancer Immunology, Immunotherapy | Issue 12/2006

Abstract

The adoptive transfer of in vitro-induced and expanded tumor-specific cytotoxic T lymphocytes (CTL) presents a promising immunotherapeutic approach for the treatment of cancer. The in vitro induction of tumor-reactive CTL requires repeated stimulation of CTL precursors with dendritic cells (DC). To circumvent problems like scarcity of blood DC precursors and donor variability, it would be attractive to use DC from a non-autologous, unlimited source. DCs derived from the human acute myeloid leukemia (AML) cell line MUTZ-3 are attractive candidates since these DCs closely resemble monocyte-derived DC (MoDC) in terms of phenotype and T cell stimulatory capacity. Here we demonstrate that functional CTL clones could be generated against multiple tumor-associated antigens, i.e., human telomerase reverse transcriptase (hTERT), ErbB3-binding protein-1 (Ebp1), carcinoembryonic antigen (CEA) and Her-2/neu, by stimulating CD8β⁺ CTL precursors with peptide-loaded allogeneic, HLA-A2-matched MUTZ-3-derived DC. A consistent induction capacity, as determined by MHC tetramer-binding, was found in multiple donors and comparable to autologous peptide-loaded MoDC. Functional characterization at the clonal level revealed the priming of CTL that recognized endogenously processed epitopes on tumor cell lines in an HLA-A2-restricted fashion. Our data indicate that MUTZ-3-derived DC can be used as stimulator cells for in vitro priming and expansion of functional TAA-specific effector CTL. MUTZ-3-derived DCs thus represent a ready and standardized source of allogeneic DC to generate CTL for therapeutic adoptive transfer strategies.

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Title: In vitro priming of tumor-specific cytotoxic T lymphocytes using allogeneic dendritic cells derived from the human MUTZ-3 cell line
Authors: Saskia J. A. M. Santegoets
Marco W. J. Schreurs
Allan J. Masterson
Ying Poi Liu
Steffen Goletz
Hans Baumeister
Esther W. M. Kueter
Sinéad M. Lougheed
Alfons J. M. van den Eertwegh
Rik J. Scheper
Erik Hooijberg
Tanja D. de Gruijl
Publication date: 01-12-2006
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 12/2006
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-006-0142-x

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