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

Eight week old female BALB/c and C3H mice were purchased from Taconic (New York, NY, USA). Tumor efficacy studies were conducted in three different syngeneic mouse models, namely colon carcinoma (CT26), bladder (MBT2) and B cell lymphoma (A20). For CT26 and A20 models, BALB/c mice were inoculated subcutaneously into the right lower flank with 1 × 10 6 cells. For MBT2 experiments, C3H mice were injected with 1 × 10 6 cells (lower right flank). Tumors were measured with calibers two times per week and tumor volumes determined using the relationship: (volume (mm 3 ) = length × width 2 /2). Mice were euthanized when tumors reached a volume of 2000 mm 3 . Randomization of mice to treatment groups occurred when mean tumor volumes reached approximately 100 mm 3 . We examined increasing dose levels of CC1 (10 and 30 mg/kg; IP, QD every other day) on tumor growth in the CT26 model. Additionally we studied the effect of anti-CEACAM1 treatment alone (CC1 30 mg/kg; IP, QD every two days) and in combination with muDX400 (5 mg/ www.oncotarget.com kg; which is a murinized version of surrogate anti-mouse PD1 mAb.; QD every 5 days) in the CT26, MBT2 and A20 models. Vehicle controls received mouse IgG1 antibody and vehicle. The dose of muDX400 was chosen based on demonstrated efficacies achieved in syngeneic mouse tumor models [25] .