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

Previous studies have provided functional evidence for tumor growth modulating activities of CEACAM1. Reduced growth of CT26 tumor cells was observed in CEACAM1 deficient mice [21] . In addition, treatment with anti-CEACAM1 Ab CC1 in combination with TIM-3 or PD-L1 blockade resulted in robust CT26 tumor growth inhibition and an increase in tumor infiltrating CD8+ T cells in the CT26 model [21] . One limitation of these prior studies is that they did not report the pharmacokinetic characteristics or the level of CEACAM1 target engagement achieved in these experiments. Our experiments found that CC1 has a relative short T1/2 in mice and associated with a rapid clearance, which in part may be related to high CEACAM1 expression on myeloid cells facilitating receptor-mediated deposition. In our in vivo syngeneic tumor models, CT26, MBT2 and A20, anti-CEACAM1 Ab CC1 administered as a single agent therapy or in combination with an anti-PD-1 mAb (muDX400), provided no tumor growth inhibition. It is important to point out that full target engagement was achieved in these in vivo experiments, based on our tumor immunophenotyping experiments showing greater than 90% suppression of cell surface CEACAM1 staining in CC1-treated animals and the fact that we maintained a plasma trough levels well above the receptor binding IC50 (at a dose of 30 mg/kg).