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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Medical oncology (Northwood, London, England). 2016 Nov 03 [Epub]
Katerina Vavrova, Petra Vrabcova, Dominik Filipp, Jirina Bartunkova, Rudolf Horvath
Department of Immunology, 2nd Medical Faculty and Faculty Hospital Motol, Charles University, V Uvalu 84, 150 06, Prague, Czech Republic., Laboratory of Immunobiology, Institute of Molecular Genetics of the AS CR, Prague, Czech Republic., Department of Immunology, 2nd Medical Faculty and Faculty Hospital Motol, Charles University, V Uvalu 84, 150 06, Prague, Czech Republic. .