CTLA4-CD28 chimera gene modification of antigen-specific CD4 T cells improves therapeutic effect of antigen-specific CD8 T cells in an antigen-expressing lymphoma model. (A) B6 mice were injected with E.G7 cells (1-2 × 106) subcutaneously. Seven days later, the mice were either left untreated or injected intravenously with EV-transduced OT-II T cells (EV; 2 × 106) or CTLA4-CD28 chimera–transduced OT-II T cells (CTC28; 2 × 106). (B) E.G7 tumor-bearing B6 mice as in panel A were either left untreated or injected intravenously with untransduced OT-I T cells (2 × 106) in combination with EV or CTC28 OT-II T cells in various ratios (0.5-2 × 106). The retrovirus-transduced T cells were rested for 48 hours in the absence of stimulus before adoptively transferred. Mean tumor size of at least 5 mice per group was recorded (*P = .0391, **P = .0078, ***P = .0078; Wilcoxon matched pairs test). Results are representative of at least 2 independent experiments.
