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. 2014 Oct 30;6(6):1560–1570. doi: 10.4161/19420862.2014.975099

Figure 4.

Figure 4.

Multivalent DR5 Nanobodies elicit robust anti-tumor responses and sustained caspase activation in vivo. (A) Dose normalized serum exposure in xenografted mice following single i.v. dose of DR5-A (20 mg/kg, COLO205), LBY135 (1 mg/kg; COLO 205) or DR5Nb1-tetra (1 mg/kg, MIA PaCa-2). (B) Caspase-8 activity following a single i.v. dose of DR5-A, DR5Nb1-tetra or DR5Nb1-penta in MIA PaCa-2 xenograft model (N = 3/group). (C) Representative cleaved caspase-8 IHC staining from the same MIA PaCa-2 xenograft at 4 hours after treatment. Scale bar = 20 μm. (D) Cleaved caspase-8 image analysis on MIA PaCa-2 tumors, 4 hours following a single 3 mg/kg i.v. dose of PBS, DR5-A, DR5Nb1-tetra or DR5Nb1-penta (N = 3/group) demonstrated more staining in all groups compared to PBS. (E) Mean tumor volume of MIA PaCa-2 tumors in xenograft bearing mice treated once with either DR5-A (3 mg/kg), DR5Nb1-tetra (3 mg/kg), DR5Nb1-penta (3mg/kg) or PBS (N = 5/group; Reg = regression). (F) Mean tumor volume of COLO 205 tumors in xenograft bearing mice treated weekly for 4 weeks with either DR5-A (3 mg/kg), DR5Nb1-tetra (3 mg/kg), DR5Nb1-penta (3 mg/kg) or PBS (N = 7/group).