Potential of TCR150-transgenic lymphocytes to retard solid tumor outgrowth in vivo. (A) Tumor outgrowth (mm2) of 4 × 105 mel624.38 cells injected SC into NSG mice at day 0 followed by adoptive transfer (IV) of mock-transduced PBLs (○; n = 6), HMMR-specific TCR150-transgenic PBLEs (●; n = 6) or HMMR-specific TCR150-transgenic PBLEMs (▴; n = 6), on day 1 at a dose of 2 × 105 TCR-transgenic PBLs per mouse (**P < .01; *P < .05). A 2-way ANOVA was used for statistical analysis. (B) Percent survival of mice treated in the experiment described in Figure 3A. Data were compared using Mantel-Cox test (*P = .001). (C) Tumor outgrowth (mm2) measured every other day after initial SC injection of 4 × 105 mel624.38 cells. TCR150-transgenic PBLEMs (2 × 105) or CD8-enriched PBLEMs were injected intravenously 1 × 24 hours later (triangle arrow to top) or 3 injections were given on 3 sequential days (mock, ○; TCR150-transgenic PBLEMs, triangle arrows to bottom; TCR150-transgenic PBLEMs + IL-15, diamonds; TCR150-transgenic CD8EM + IL-15, ●). Administration of IL-15 (10 μg/mouse/d) intraperitoneally for 10 days was started 24 hours after tumor inoculation. The outgrowth was significantly retarded compared with mock treatment in the following magnitude: TCR150-transgenic TBLEMs1× < TCR150-transgenic PBLEM3× < TCR150-transgenic PBLEM3× + IL-15 < TCR150-transgenic CD8EM3× + IL-15 (**P < .01; ***P < .001 by 2-way ANOVA). (D) Survival of mice shown in panel C. Mean survival was correlated with retardation of tumor growth as follows: mock-treated PBLEMs, 23 days; TCR150-transgenic PBLEM1×, 32 days; TCR150-transgenic PBLEM3×, 37 days; TCR150-transgenic PBLEM3× + IL-15, 37 days; and TCR150-transgenic CD8EM3× + IL-15, 60 days. All treatments showed significantly prolonged survival compared with mock treatment (P < .03 by Mantel-Cox test), whereas only treatment with CD8-enriched PBLEM (3×) and IL-15 IP yielded significant prolongation compared with mice treated with TCR150-transgenic PBLEM1× (n = 6 per group; *P < .03 by Mantel-Cox test).
