Figure 4

Effect of T-DM1 on the formation of JIMT-1 xenografts. SCID mice injected s.c. with 5 × 10⁶ JIMT-1 cells were treated on a weekly basis with control antibody (rituximab, 5 mg/kg, i.p., black circle, n = 7), trastuzumab (5 mg/kg, i.p., red triangle, n = 6), T-DM1 (5 mg/kg, i.v., green triangle, n = 6) or on a daily basis with lapatinib (100 mg/kg, p.o., brown circle, n = 7) starting from the day of tumour inoculation (Day 0). Drug administration schedule is shown by arrows. Lapatinib (brown circle) had no effect on tumour growth. Trastuzumab (red triangle) reduced the formation of tumours between days 6 and 34 compare to both control antibody and lapatinib (red stars, P < 0.05). In three out of the six trastuzumab treated mice, trastuzumab administration was suspended and switched to T-DM1 (5 mg/kg, i.v., yellow square) from the Day 41 (marked by white arrow) whereas it was continued for another three weeks in the other three (5 mg/kg, i.p., blue square). In this setting, T-DM1 was unable to inhibit tumour growth. The tumours started to grow in four T-DM1 treated mice (green triangle) from Day 55 onward, but remained non-palpable in two (2/6). T-DM1 administration of these two mice was suspended on Day 76 (marked by Ο) and the mice were followed up for more four weeks (pale blue square, n = 2). In these two mice, a very small palpable tumour (approximately 4 mm³) was detected in one mouse on Day 107 and residual cancer cells were found histologically. No tumour was detected in the other mouse and the histological examination of the tumour inoculation site suggested a complete cure. T-DM1 treatment of the other four mice was continued until the end of the experiment (5 mg/kg, i.v., pink square, n = 4). Overall, T-DM1 significantly inhibited the tumour formation from Day 13 to Day 34 in comparison to both control antibody and lapatinib (green stars, P < 0.05), and it had a significantly growth inhibition between days 13 and 62 compared to trastuzumab (green a, P < 0.05). Note that both trastuzumab and T-DM1 were used in a dose of 5 mg/kg.