Figure 6. Pathway sensitization reveals the full potential of MUC16-targeted Meso64-TR3 in both TRAIL sensitive and refractory cancer cells.
Cell viability determinations were performed on TRAIL sensitive OVCAR3 cells (A. and B. 100% MUC16) and the TRAIL refractory cells HPAC (C. and D. 50% MUC16) and HeLa (E. and F. 60%- 80% MUC16). In order to illustrate the benefit of MUC16 targeting, OVCAR3 cells were treated with TR3 (A), Meso64-TR3 (B) and SW IV-134 (A, B) alone and in combination with each other at increasing concentrations of both cancer drugs. Please note that the drug concentrations required to achieve close to 100% target cell death using combination therapy (solid arrows) are much reduced for Meso64-TR3 compared to the drugs used in isolation (open arrow). The killing capacities of TR3 and Meso64-TR3 were also studied on cells that were refractory to TRAIL treatment in the absence (C; HPAC, NS, not significant and E; HeLa, NS, not significant) and in the presence of pathway sensitization using constant doses of SW IV-134 (D; HPAC, **P < 0.004 and F; HeLa, **P < 0.003).