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.

• Klíčová slova
• Adoptive T cell therapy, Cancer immunotherapy, Prostate cancer, Tumor-specific T cell expansion,
• MeSH
• aktivace lymfocytů MeSH
• antigeny nádorové imunologie   MeSH
• bioreaktory MeSH
• dendritické buňky imunologie   MeSH
• epitopy T-lymfocytární imunologie   MeSH
• imunoterapie adoptivní metody   MeSH
• interferon gama biosyntéza   imunologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory prostaty imunologie   MeSH
• nádory vaječníků imunologie   MeSH
• regulační T-lymfocyty imunologie   MeSH
• studie případů a kontrol MeSH
• T-lymfocyty - podskupiny imunologie   MeSH
• T-lymfocyty imunologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny nádorové MeSH
• epitopy T-lymfocytární MeSH
• interferon gama MeSH