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Generation of T cell effectors using tumor cell-loaded dendritic cells for adoptive T cell therapy
K. Vavrova, P. Vrabcova, D. Filipp, J. Bartunkova, R. Horvath,
Language English Country United States
Document type Journal Article
NLK
ProQuest Central
from 1997-03-01 to 2017-12-31
Medline Complete (EBSCOhost)
from 2013-03-01 to 1 year ago
Health & Medicine (ProQuest)
from 1997-03-01 to 2017-12-31
- MeSH
- Lymphocyte Activation MeSH
- Antigens, Neoplasm immunology MeSH
- Bioreactors MeSH
- Dendritic Cells immunology MeSH
- Epitopes, T-Lymphocyte immunology MeSH
- Immunotherapy, Adoptive methods MeSH
- Interferon-gamma biosynthesis immunology MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Prostatic Neoplasms immunology MeSH
- Ovarian Neoplasms immunology MeSH
- T-Lymphocytes, Regulatory immunology MeSH
- Case-Control Studies MeSH
- T-Lymphocyte Subsets immunology MeSH
- T-Lymphocytes immunology MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Adoptive T cell transfer has been shown to be an effective method used to boost tumor-specific immune responses in several types of malignancies. In this study, we set out to optimize the ACT protocol for the experimental treatment of prostate cancer. The protocol includes a pre-stimulation step whereby T cells were primed with autologous dendritic cells loaded with the high hydrostatic pressure-treated prostate cancer cell line, LNCaP. Primed T cells were further expanded in vitro with anti-CD3/CD28 Dynabeads in the WAVE bioreactor 2/10 system and tested for cytotoxicity. Our data indicates that the combination of pre-stimulation and expansion steps resulted in the induction and enrichment of tumor-responsive CD4(+) and CD8(+) T cells at clinically relevant numbers. The majority of both CD4(+) and CD8(+) IFN-γ producing cells were CD62L, CCR7 and CD57 negative but CD28 and CD27 positive, indicating an early antigen experienced phenotype in non-terminal differentiation phase. Expanded T cells showed significantly greater cytotoxicity against LNCaP cells compared to the control SKOV-3, an ovarian cancer line. In summary, our results suggest that the ACT approach together with LNCaP-loaded dendritic cells provides a viable way to generate prostate cancer reactive T cell effectors that are capable of mounting efficient and targeted antitumor responses and can be thus considered for further testing in a clinical setting.
References provided by Crossref.org
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- $a Adoptive T cell transfer has been shown to be an effective method used to boost tumor-specific immune responses in several types of malignancies. In this study, we set out to optimize the ACT protocol for the experimental treatment of prostate cancer. The protocol includes a pre-stimulation step whereby T cells were primed with autologous dendritic cells loaded with the high hydrostatic pressure-treated prostate cancer cell line, LNCaP. Primed T cells were further expanded in vitro with anti-CD3/CD28 Dynabeads in the WAVE bioreactor 2/10 system and tested for cytotoxicity. Our data indicates that the combination of pre-stimulation and expansion steps resulted in the induction and enrichment of tumor-responsive CD4(+) and CD8(+) T cells at clinically relevant numbers. The majority of both CD4(+) and CD8(+) IFN-γ producing cells were CD62L, CCR7 and CD57 negative but CD28 and CD27 positive, indicating an early antigen experienced phenotype in non-terminal differentiation phase. Expanded T cells showed significantly greater cytotoxicity against LNCaP cells compared to the control SKOV-3, an ovarian cancer line. In summary, our results suggest that the ACT approach together with LNCaP-loaded dendritic cells provides a viable way to generate prostate cancer reactive T cell effectors that are capable of mounting efficient and targeted antitumor responses and can be thus considered for further testing in a clinical setting.
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- $a Horvath, Rudolf $u Department of Immunology, 2nd Medical Faculty and Faculty Hospital Motol, Charles University, V Uvalu 84, 150 06, Prague, Czech Republic. rudolf.horvath@lfmotol.cuni.cz. Department of Pediatric and Adult Rheumatology, Faculty Hospital Motol, Prague, Czech Republic. rudolf.horvath@lfmotol.cuni.cz.
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