Differential in vivo antitumor potency of tumor-specific human primary T cells overexpressing IL-2, IL-7, IL-15, or IL-21. NOD/SCID/γcnull mice were inoculated with 5 × 105 Raji-GL tumor cells and 6 days later received adoptive transfer of 2 × 105 19z1+CD8+ T cells transduced with 19z1-ΔLNGFR (n = 23), 19z1-IL2 (n = 23), 19z1-IL7 (n = 24), 19z1-IL15 (n = 23), 19z1-IL21 (n = 23), or no T cells (n = 14). As nonspecific controls, mice received T cells transduced with Pz1-ΔLNGFR, Pz1-IL2, Pz1-IL7, Pz1-IL15, or Pz1-IL21 vectors (n = 4 each). The percentage of 19z1+ T cells for each of the 3 experiments at the time of adoptive transfer was as follows: 19z1-ΔLNGFR: 53, 71, 61 (mean, 62); 19z1-IL2: 62, 64, 72 (mean, 66); 19z1-IL7: 81, 92, 85 (mean, 86); 19z1-IL15: 63, 68, 72 (mean, 68); and 19z1-IL21: 72, 78, 76 (mean, 75). (A) Quantified tumor burden measured by in vivo bioluminescent imaging. Immediately prior to T-cell injection, biweekly until day 55, and weekly thereafter, mice were anesthetized and administered intraperitoneal d-luciferin (150 mg/kg), and ventral tumor burden was assessed by the Xenogen 100 in vivo imaging system. Mice were imaged up to 3 at a time, separated by opaque shields. Saturated luminescent signals were imaged for shorter durations, down to 2 seconds. Each black line represents 1 animal; dots along the line indicate an imaging time point. The thick red line represents the average tumor burden of mice that received PSMA-specific T cells. Fractions in the lower right corner of each graph represent the proportion of 19z1-treated surviving mice at day 106. Bioluminescent images from 3 representative mice from 1 experiment at day 27 after tumor challenge are shown. 19z1 data are from 3 pooled experiments (n = 5-10), each testing T cells from a different donor. (B-C) Efficacy of tumor immunotherapy with cytokine-transduced T cells. Kaplan-Meier survival curves depicting overall survival (B), and tumor-free survival (C) in which mice were considered tumor free if their tumor burden was < 104 photons/s/cm2/sr. Pz1-ΔLNGFR/cytokine refers to the combined survival of all mice treated with PSMA-specific T cells. *P < .05, #P < .005 versus 19z1-ΔLNGFR.