Anti-ATL reactivity of hTERT-siTCR–transduced CD8+ T cells in vivo. (A) Winn assay. NOG mice were coinjected with a luciferase-transduced HLA-A*24:02+ ATL cell line (ATN-1/luc) (5 × 105) and either 2.5 × 106 hTERT-siTCR–transduced (hTERT-siTCR/CD8) or NGM/CD8+ T cells (n = 2 per group). Subsequently, 3 weekly infusions of the respective CD8+ T-cell populations (2.5 × 106 cells per infusion) were administered intravenously (i.v.). Tumor growth was monitored every 7 days by using bioluminescence assay. Nontreated ATN-1/luc cells were similarly inoculated into NOG mice (n = 2) as a control. Although NGM/CD8 activated using OKT-3 and rhIL-2 suppressed tumor growth to some extent, hTERT-siTCR/CD8 durably suppressed tumor growth for longer than 6 months. (B) Therapeutic adaptive transfer model. NOG mice were intravenously inoculated with 5 × 105 ATN-1/luc cells. Four days later, intravenous administration of either 5 × 106 hTERT-siTCR/CD8 or NGM/CD8 (n = 2 per group) was started once a week for a total of 5 infusions. NOG mice given only ATN-1/luc cells (n = 2) were used as a control. In comparison with NGM/CD8, therapeutically infused hTERT-siTCR/CD8 also obviously suppressed the tumor cell growth within the 8-week observation period. Serial images of the bioluminescence assay demonstrate tumor growth in each group.
