Generation of T cell effectors using tumor cell-loaded dendritic cells for adoptive T cell therapy

0471910 - ÚMG 2017 RIV US eng J - Článek v odborném periodiku
Vávrová, K. - Vrabcova, P. - Filipp, Dominik - Bartunkova, J. - Horváth, R.
Generation of T cell effectors using tumor cell-loaded dendritic cells for adoptive T cell therapy.
Medical Oncology. Roč. 33, č. 12 (2016), č. článku 136. ISSN 1357-0560. E-ISSN 1559-131X
Grant CEP: GA ČR(CZ) GBP302/12/G101
Institucionální podpora: RVO:68378050
Klíčová slova: Cancer Immunotherapy * Prostate cancer * Adoptive T cell therapy * Tumor-specific T cell expansion
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 2.634, rok: 2016

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-gamma 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.
Trvalý link: http://hdl.handle.net/11104/0269283