Anti–human CTLA-4 antibodies with different potency in delaying tumor growth. (A) Growth kinetics of MC38 tumors in minimal disease model. CTLA-4 (hu/hu) mice were challenged with MC38 (5 × 105/mouse) in the lower abdomen. Two days later, the mice received either control mouse IgG or anti–CTLA-4 antibodies K4G4, L1B11, or L3D10 and the tumors were measured every 3 to 4 days. Data shown represent means and standard error of the mean (SEM) of tumor volumes until day 55, when some mice in antibody-treated groups reached their tumor burden end point (n=4). (B) Log transformation of tumor volume. The tumor growth over time was analyzed using the StataR XTGEE (cross-sectional generalized estimating equations) model. Six tests were done to compare the exponential slopes. All mAbs significantly delayed the growth kinetics of tumors (P < .001). In addition, significant delay of tumor growth was observed in mice that received L3D10 in comparison to those that received either L1B11 or K4G4 (P < .001). (C) Kaplan-Meier survival curves of mice that received either control IgG or one of the anti–CTLA-4 antibodies. Complete rejection of tumors was observed in 2 of 9 mice in the L3D10-treated group. A log-rank test revealed that the 3 mAbs significantly prolonged mouse survival (P < .001–P = .004). Data shown in panels A and B are representative of those from 2 independent experiments. Data in panel C involve 8 to 9 mice per group.
