Novel mode of action of c-kit tyrosine kinase inhibitors leading to NK cell–dependent antitumor effects
J. Clin. Invest. Christophe Borg, et al. 114:379 doi:10.1172/JCI21102 [Go to this article.]

Figure 2
Gleevec promoted NK cell–dependent antitumor effects. (A and B) FL and Gleevec synergize to prevent RMA-S tumor establishment. In one abdominal flank of C57BL/6 mice, TAP-deficient RMA-S cells were injected (A), whereas TAP-sufficient RMA cells were injected into the other flank of the same mice (B). The same number of cells of each type were injected (10⁶ cells). From 6 days before injection (day –6) to day 3, FL (10 μg/day) or PBS (200 μl) was injected intraperitoneally. From day 1 to day 4, Gleevec (150 mg/kg bid) or H₂O (200 μl) was administered orally. The number of tumor-free mice at the end of the experiment is indicated in parentheses. Each experiment included 5 mice per group and was repeated twice with similar results. (C) The antitumor effects of Gleevec against B16F10 lung metastases are mediated by NK cells. Neutralizing anti-NK1.1 mAb (300 μg of PK136 mAb/mouse) or normal mouse serum (NMS) were administered intraperitoneally at days –4, -–2, 0, and 4 in C57BL/6 mice. At day 0, 5 × 10⁵ B16F10 tumor cells were inoculated into the tail vein. Oral feeding with Gleevec (150 mg/kg bid) or H₂O (200 μl) was administered on days 5–11, and mice were sacrificed for the enumeration of lung metastases at day 11. The results of one representative experiment (of 2) including 5–7 mice per group are shown. The Kruskal Wallis multiple comparison test was used to compare the number of lung metastases (*P < 0.05 between Gleevec and H₂O in NMS groups; **P < 0.01 between NMS and anti-NK1.1 mAb in Gleevec groups; there was no significant difference between H₂O and Gleevec in anti-NK1.1 mAb groups).