Figure 4

Synergy of concurrent treatment with anti-TRAIL receptor antibodies and cisplatin. Concurrent treatment with Lexatumumab (Lexa) monoclonal antibody enhances the activity of cisplatin in ZL5 MPM cells. ZL5 MPM cells were treated with single treatments or combinations of 2.12 μM cisplatin and/or 1.01 μg/ml Lexatumumab or fractions/multiples of those concentrations at a constant ratio from 0.25- to 4-fold. Responses were determined by MTT assay after 72 h and bars indicate standard deviations. Synergy was quantified by Combination Index (CI) analysis and expressed as CI versus fraction affected. By this method, CI<1 indicates synergy; CI = 1 indicates an additive effect; and CI>1 indicates antagonism. 96% confidence intervals are shown on CI plots. Data shown represent mean values from three independent experiments. B and C. Concurrent treatment with Mapatumumab (Mapa) or Lexatumumab monoclonal antibodies enhance the cytotoxicity of cisplatin in H28 cells. Experiments were performed as described under A, except that cisplatin, Mapatumumab and Lexatumumab were used at a concentration of 6.61 μM, 0.13 μg/ml and 0.40 μg/ml, respectively, and fractions/multiples thereof. Data represent means of three independent experiments and bars indicate standard deviations.