Figure 1.
Lymphodepletion enhances antitumor efficacy of adoptively transferred CD8+ T cells. (a) 5 Gy TBI induces severe lymphopenia. Mice were treated with 5 Gy TBI or a nonmyeloablative chemotherapy regimen with 250 mg/kg Cytoxan + 50 mg/kg fludarabine. Absolute lymphocyte count was determined at the indicated time points. (b) Lymphodepletion augments antitumor responses. TBI or nonirradiated WT mice bearing 12-d-old established s.c. B16 tumors were left untreated or received adoptive transfer of 106 cultured pmel-1 T cells in conjunction with rFPhgp100 vaccination and rhIL-2. Data shown are representative of multiple independent experiments. Values represent the mean ± SEM. (c–e) Lymphodepletion does not result in increased numbers of adoptively transferred T cells. Absolute numbers of adoptively transferred pmel-1 cells (CD8+Thy1.1+) in the spleens (c) and in the blood (d) of tumor-bearing, TBI, and nonirradiated mice. Percentages of adoptively transferred pmel-1 cells (CD8+Thy1.1+) in the tumor (e) under conditions specified. (f–i). Lymphodepletion enhances effector functions of adoptively transferred T cells. 6 d after adoptive transfer, pmel-1 thy1.1+ cells were isolated from the spleens of irradiated and nonirradiated mice and co-cultured with irradiated splenocytes pulsed with the indicated doses of hgp10025–33. Unpulsed splenocytes were used as controls. Data shown are representative of two independent experiments.