Potent immunotherapy against well-established thymoma using adoptively transferred transgene IL-6-engineered dendritic cell-stimulated CD8+ T-cells with prolonged survival and enhanced cytotoxicity

Background Adoptive transfer of CD8(+) T-cells specific for tumor-antigens is an attractive strategy for anti-tumor therapy. In the present study, the subsets T-A and T-B were used to represent the population of CD8(+) T cells generated by culturing the respective cells with irradiated dendritic cells (DCs) pulsed with ovalbumin (OVA) protein and transfected with adenoviral vector constructs as described. Methods Naive OVA specific CD8(+) T cells were isolated from the spleen of OVA-specific T-cell receptor transgenic OTI mice. The subsets T-A and T-B were then generated by in vitro activating the population of CD8(+) T cells with OVA-pulsed DCs transfected with IL-6-expressing adenoviral vector (AdV(IL-6)) or the control vector (AdV(Null)). To assess their in vivo immunotherapeutic effects, T-A-or T-B-cells were intravenously transferred into C57BL/6 mice bearing EG7 thymoma (6-8mm in diameter). Results T-A-cells displayed a higher level of expression of CD62 l, IL-7R, FasL, perforin and CCR6, and also exhibited more potent in vitro cytotoxicity to OVA-expressing EG7 thymoma cells via perforin-and Fas/FasL-mediated apoptosis than T-B-cells. CD8(+) T-cell survival was kinetically analyzed in C57BL/6 mice transferred with T-A-or T-B-cells by flow cytometry. We found that the adoptively transferred T-A-cells had prolonged survival and enhanced T-cell memory development compared to T-B-cells. In addition, T-A-, but not T-B-cells were able to eradicate well-established EG7 thymomas in all eight tumor-bearing mice. Conclusions Our data suggest that AdVIL-6-transfected DC-stimulated CD8(+) T cells with potent cytotoxicity and survival advantage may serve as an effective adoptive CD8(+) T-cell immunotherapy strategy for anti-tumor treatment. Copyright (C) 2015 John Wiley & Sons, Ltd.