Characterization of murine CEACAM1 in vivo reveals low expression on CD8(+) T cells and no tumor growth modulating activity by anti-CEACAM1 mAb CC1

McLeod, Robbie L.; Angagaw, Minilik H.; Baral, Toya Nath; Liu, Liming; Moniz, Raymond Joseph; Laskey, Jason; Hsieh, SuChun; Lee, Mike; Han, Jin-Hwan; Issafras, Hassan; Javaid, Sarah; Loboda, Andrey; Sadekova, Svetlana; O'Connor, Joann A.; Tse, Archie; Punnonen, Juha

To profile the impact of CC1 alone as a single agent and study the potential combinational effect with an anti-PD-1 antibody (muDX400), we utilized three subcutaneous mouse tumor models, CT26 (colorectal), MBT2 (bladder) and A20 (B cell lymphoma). CC1 (10-30 mg/kg) treatment with and without muDX400 (5 mg/kg) was well tolerated with no effects on mouse body weights across models and throughout the duration of each study (data not shown). In the CT26 experiments baseline tumor volumes for the control group at randomization were 100 mm 3 and were not different from the treatment groups. By day 11, CT26 tumors in the control group increased approximately 20-fold. Figure 4 shows that CC1 (10 and 30 mg/kg, i.p.) administered every other day did not significantly attenuate tumor growth relative to controls. In contrast, muDX400 treatment (5 mg/kg, i.p. given every 4 days) inhibited tumor volume on day 11 by approximately 40-50%. There was no modulation of the muDX400 growth curve by co-administration of CC1 (30 mg/kg) indicating no observable combination benefit were randomized into 5 treatment groups of 16 mice per group: (1) isotype control + vehicle control; (2) muDX400 (5 mg) + vehicle control; (3) isotype control + CC1 (10 mg/kg); (4) isotype control + CC1 (30 mg/kg) and (5) muDX400 (5 mg/kg) +CC1 (30 mg/kg). Significant anti-tumor activity was observed in the muDX400 (5 mg/kg) and muDX400 plus CC1 (30 mg/kg) combination arms as compared to controls. A significant difference was not observed between CC1 (10 and 30 mg/kg) treatment and control treatment. P < 0.05 (Kruskal-Wallis in conjunction with Mann-Whitney U post hoc analysis) compared to control at day 11. in this model. Similarly, no obvious combination activity with muDX400 and CC1 were demonstrated in either the MBT2 or A20 model ( Figure 5 ).