Generation of T cell effectors using tumor cell-loaded dendritic cells for adoptive T cell therapy.
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.
Department of Immunology, 2nd Medical Faculty and Faculty Hospital Motol, Charles University, V Uvalu 84, 150 06, Prague, Czech Republic.
Katerina
K
Vavrova
Department of Immunology, 2nd Medical Faculty and Faculty Hospital Motol, Charles University, V Uvalu 84, 150 06, Prague, Czech Republic.
Petra
P
Vrabcova
Laboratory of Immunobiology, Institute of Molecular Genetics of the AS CR, Prague, Czech Republic.
Dominik
D
Filipp
Department of Immunology, 2nd Medical Faculty and Faculty Hospital Motol, Charles University, V Uvalu 84, 150 06, Prague, Czech Republic.|Sotio, Prague, Czech Republic.
Jirina
J
Bartunkova
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.
Rudolf
R
Horvath
D000951:Antigens, Neoplasm / Q000276:immunology; D019149:Bioreactors; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D010051:Ovarian Neoplasms / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma
Adoptive T cell therapy; Cancer immunotherapy; Prostate cancer; Tumor-specific T cell expansion