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. 2023 Jun 2;29(16):2988–3003. doi: 10.1158/1078-0432.CCR-23-0974

Figure 2.

Figure 2. In vitro and in vivo antitumor activity. A, Representative dose-dependent binding of bivalent, trivalent (TRAIL), tetravalent (INBRX-109), and hexavalent anti-DR5 molecules on H-EMC-SS chondrosarcoma cells. B, Impact of valency on H-EMC-SS cell death. Death of H-EMC-SS cells 16 hours after treatment with the indicated concentrations of molecules of increasing valency was measured by CellTiter-Glo. Data were fit with a nonlinear four-parameter agonist concentration versus response curve, and calculated EC50 values are reported. Activity of INBRX-109 was assessed in the presence of the pan-caspase inhibitor Z-VAD-FMK. C, Impact of valency on potency. The fold improvement in potency from bivalent to trivalent, trivalent to tetravalent, and tetravalent to hexavalent is shown. D, Activation of caspase-3 and -7 in H-EMC-SS cells treated with bivalent, trivalent (TRAIL), tetravalent (INBRX-109), and hexavalent anti-DR5 molecules for the indicated durations of time was measured by real-time imaging on an Incucyte live cell imaging system. Activity of INBRX-109 was assessed in the presence or absence of the pan-caspase inhibitor Z-VAD-FMK. E, Tumor volume over time in animals harboring patient-derived chondrosarcoma tumors and treated with vehicle or INBRX-109 (1 mg/kg, i.v. once every week × 3 weeks starting on study day 0, as indicated by arrows). Each symbol represents the mean tumor volume of 8 animals, with error bars to denote SEM. Abbreviations: DR5, death receptor 5; Kd, equilibrium dissociation constant.

In vitro and in vivo antitumor activity. A, Representative dose-dependent binding of bivalent, trivalent (TRAIL), tetravalent (INBRX-109), and hexavalent anti-DR5 molecules on H-EMC-SS chondrosarcoma cells. B, Impact of valency on H-EMC-SS cell death. Death of H-EMC-SS cells 16 hours after treatment with the indicated concentrations of molecules of increasing valency was measured by CellTiter-Glo. Data were fit with a nonlinear four-parameter agonist concentration versus response curve, and calculated EC50 values are reported. Activity of INBRX-109 was assessed in the presence of the pan-caspase inhibitor Z-VAD-FMK. C, Impact of valency on potency. The fold improvement in potency from bivalent to trivalent, trivalent to tetravalent, and tetravalent to hexavalent is shown. D, Activation of caspase-3 and -7 in H-EMC-SS cells treated with bivalent, trivalent (TRAIL), tetravalent (INBRX-109), and hexavalent anti-DR5 molecules for the indicated durations of time was measured by real-time imaging on an Incucyte live cell imaging system. Activity of INBRX-109 was assessed in the presence or absence of the pan-caspase inhibitor Z-VAD-FMK. E, Tumor volume over time in animals harboring patient-derived chondrosarcoma tumors and treated with vehicle or INBRX-109 (1 mg/kg, i.v. once every week × 3 weeks starting on study day 0, as indicated by arrows). Each symbol represents the mean tumor volume of 8 animals, with error bars to denote SEM. Abbreviations: DR5, death receptor 5; Kd, equilibrium dissociation constant.