IFN-γ– and perforin-dependent inhibition of established lung metastases by T-scFv-CD28-ζ cell transfer.

The survival of groups of 10 scid mice injected intravenously with erbB2⁺ human MDA-MB-435 breast carcinoma cells (5 × 10⁶ cells). Mice were injected intravenously with a single dose (10⁷) of BALB/c WT T cells transduced with the pLXSN vector alone (■), scFv-anti-erbB2-ζ chimera (●), or scFv-anti-erbB2-CD28-ζ chimera (○) one day (A) or 5 days (B) after tumor inoculation. (C) Alternatively, mice were also injected intravenously with 10⁷ T-scFv-anti-erbB2-ζ cells (closed symbols) or T-scFv-anti-erbB2-CD28-ζ cells (open symbols) from BALB/c WT (circles), pfp^−/− (triangles), IFN-γ^−/− (squares), and pfp^−/−IFN-γ^−/− (diamonds) mice on day 1 after tumor inoculation. Control scid mice inoculated with MDA-MB-435 tumor cells received no T-cell treatment (crosses). (D) Treatment using WT T cells as in (A) and (B) 10 days after tumor inoculation. Control scid mice inoculated with MDA-MB-435 tumor cells received no treatment (▪). Results are representative of 2 experiments and are calculated as the percentage of each group surviving; arrows depict the days of T-cell transfer. Tumor-free mice treated with the same dose and strain of T cells were compared (T-scFv-CD28-ζ and T-scFv-ζ receptors) and statistically evaluated by Fisher exact test (*P ≤ .05, **P ≤ .01).