Fig. 4.

ABT-199 induces complete tumor regression when given in combination with cyclophophosphamide to aggressive murine models of HR NB. NB cell line xenografts representing Bcl-2 dependent (NB-1643) and Mcl-1 dependent (IMR5) subclasses were established in the flank of nu/nu athymic mice. Mice with tumors 150–200 mm³ were randomized to receive either intraperitoneal cyclophosphamide (CPM), oral ABT-199 (A), Cyclophosphamide + ABT-199 (CPM + A), or vehicle control (C), as outlined in Methods. Waterfall plot of individual tumor volume as % volume change from tumor volume pre-therapy are depicted for IMR5 (a) and NB1643 (b) tumors. Negative values define best-response tumor shrinkage with −100 % representing complete regression. Kaplan-Meier curves comparing survival of control (black) versus ABT-737 (blue), and CPM (red) versus CPM + ABT-199 (green) in representative xenografts of IMR5 (c) and NB1643 (d). p-values derived using the log-rank test. For NB-1643, n = 10 mice per arm; for IMR5, n = 9 mice per arm