Fig. 4.
In vivo efficacy studies of P-SMAC. (A) In the prophylactic model, 1 × 106 C4-2 cells were mixed with 2 × 106 PBMCs (1:2 ratio) in 50% Matrigel and were injected s.c. into the right shoulder of male NOD-SCID mice. P-SMAC, unconjugated Fab, or PBS (vehicle) (n = 6) was administered i.v. at 2 mg/kg every day for 10 d starting on day 4. Tumors were monitored by external caliper measurements at regular intervals for 6 wk. P-SMAC suppressed tumor growth, but the control groups rapidly developed tumors. *Mice with large tumors (>1,000 mm3) were killed before the day indicated. (B) In the treatment model, 1 × 106 C4-2 cells with 50% Matrigel were injected s.c. into male NOD/SCID-γ mice. On day 3, 20 × 106 hPBMCs were injected i.p. PBMCs from the same donor were activated ex vivo by incubation with immobilized αCD3 and αCD28 antibodies for 3 d and subsequently were expanded with rh-IL2. Once the solid tumors were palpable (day 13), 20 × 106 activated hPBMCs were injected i.p. Beginning on day 15, 1 mg/kg P-SMAC or PBS was given daily for 10 d i.v. (n = 9). (**P < 0.0001.)