Expansion of T cells in the presence of idelalisib and/or VIPhyb significantly enhances their anti-tumor activity in a murine lymphoma model. OT-I, OT-II, and B6 T cells were expanded for 3 days using anti-CD3/CD28 beads in the presence or absence of idelalisib and/or VIPhyb. Cells were then mixed (2 OT-I:1 OT-II:2 B6 ratio) and injected into B6 SJL mice bearing subcutaneous E.G7 OVA tumors. Growth of tumors was monitored by caliper measurement with volume calculated as (length × width²)/2. (A) Experimental outline. (B) Flow plots showing the phenotype of T cells on day 3 of expansion just prior to injection into tumor-bearing mice. (C) Histogram showing the expression of CD62L on T cells on day 3 of expansion. Blue, DMSO; green, 100 nM idelalisib; purple, 3 μM VIPhyb; red, Idelalisib + VIPhyb. (D) Tumor growth curve and quantification of tumor volume on the final day of allowable growth. (E) Images of tumors removed from sacrificed mice on day 18 of growth. Note that the tumor from 1 mouse from the idelalisib + VIPhyb group regressed and was undetectable. (F) Survival curve of tumor-bearing mice receiving T cells expanded under the indicated conditions. **P < .01; n = 4 or 5 mice per group from 2 independent experiments.