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Table 1 Therapeutic effect of H-Zt/g4-MMAE in comparison with H-Zt/g4-DM1 in inhibition of xenograft tumors derived from human pancreatic and colorectal cancer cellsa

From: Therapeutic efficacy, pharmacokinetic profiles, and toxicological activities of humanized antibody-drug conjugate Zt/g4-MMAE targeting RON receptor tyrosine kinase for cancer therapy

Anti-RON ADCs Evaluated

Tumor growth inhibition based on average tumor weights (gram)

Colorectal Cancer

Pancreatic cancer

 

LoVo

HCT116

HT29

SW620

Pan-1

BxPc-3

FG

L3.6pl

M-Zt/g4-DM1

ND

D16/D16:6.23/156 (96.02%)

D16/D16:5.92/180 (96.67%)

D16/D16:110/624 (82.37%)

ND

D32/D32: 0.06/0.7 (91.8%)

D20/D32: 1.89/2.49 (24.1%)

D16/D28: 1.41/2.54 (44.6%)

H-Zt/g4-DM1

D36/D36: 1.11/1.0 (9.01%)

D36/D36: 0.32/1.88 (82.98%)

D32/D36: 0.21/1.71 (87.72%)

D36/D36: 0.14/1.95 (92.82%)

D32/D32 1.25/1/32 (−5.30%)

D32/D32 0.08/0.81 (90.12%)

D32/d32 1.67/2.33 (28.33%)

D32/D32 1.31/2.44 (46.31%)

M-Zt/g4-MMAE

ND

ND

ND

ND

D44/44: 0.44/0,41 (−7.32)

D44/D52: 0.01/1.19 (99.2%)

D24/D44: 0.03/1.54 (98.1)

D24/D44: 0.02/1.58 (98.7)

H-Zt/g4-MMAE

D44/D44: 1.33/1.56 (14.7%)

D36/D52: 0.01/2.12 (99.5%)

D32/D52: 0.01/1.76 (99.4%)

D36/D52: 0.02/1.63 (98.8%)

D44/D44: 1.29/1.3 (3.70%)

D40/D52: 0.01/1.97 (99.9%)

D28/D52: 0.01/1.62 (99.4%)

D28/D52: 0.01/2.0 (99.5%)

  1. aAnti-RON ADCs including mouse (M)-Zt/g4-DM1, H-Zt/g4-DM1, M-Zt/g4-MMAE, and H-Zt/g4-MMAE were prepared according to methods detailed in a previous report [31] and in Experimental Procedures. The drug to antibody ratios for each ADC are 3.72:1 for M-Zt/g4-DM1, 3.83:1 for H-Zt/g4-DM1, 3.67:1 for M-Zt/g4-MMAE, and 3.77:1 for H-Zt/g4-MMAE, respectively. CRC and PDAC xenografts in mouse model were established as detailed in Experimental Procedures. Individual ADCs were used at 20 mg/kg in the Q12 × 2 schedules. At the end of the study dependent on growth rate of individual models, tumors were collected and weighted to reach an average value for each group. The percentages of inhibition for tumor growth were calculated as detailed in Experimental Procedures
  2. The percentages of inhibition were highlighted in bold
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