In vitro priming of tumor-specific cytotoxic T lymphocytes using allogeneic dendritic cells derived from the human MUTZ-3 cell line
| Autor: | Hans Baumeister, Saskia J. A. M. Santegoets, Erik Hooijberg, Ying Poi Liu, Sinéad M. Lougheed, Alfons J.M. van den Eertwegh, Steffen Goletz, Marco W.J. Schreurs, Allan J. Masterson, Esther W. M. Kueter, Tanja D. de Gruijl, Rik J. Scheper |
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| Přispěvatelé: | Internal medicine, Pathology |
| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Adoptive cell transfer Receptor ErbB-2 T cell Immunology Priming (immunology) Biology Major histocompatibility complex Immunotherapy Adoptive Antigens Neoplasm Cell Line Tumor Neoplasms HLA-A2 Antigen medicine Humans Immunology and Allergy Cytotoxic T cell Antigen-presenting cell Telomerase Adaptor Proteins Signal Transducing RNA-Binding Proteins Dendritic Cells Dendritic cell Carcinoembryonic Antigen Clone Cells CTL medicine.anatomical_structure Oncology Cancer research biology.protein T-Lymphocytes Cytotoxic |
| Zdroj: | Santegoets, S J A M, Schreurs, M W J, Masterson, A J, Liu, Y P, Goletz, S, Baumeister, H, Kueter, E W M, Lougheed, S M, Van Den Eertwegh, A J M, Scheper, R J, Hooijberg, E & De Gruijl, T D 2006, ' In vitro priming of tumor-specific cytotoxic T lymphocytes using allogeneic dendritic cells derived from the human MUTZ-3 cell line ', Cancer Immunology, Immunotherapy, vol. 55, no. 12, pp. 1480-1490 . https://doi.org/10.1007/s00262-006-0142-x Cancer Immunology, Immunotherapy, 55(12), 1480-1490. Springer Science and Business Media Deutschland GmbH |
| ISSN: | 1432-0851 0340-7004 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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