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

There has been an increasing interest by the oncology community to explore CEACAM1 as a potential target for cancer immunotherapy given its expression on tumor and immune cells and its potential immunomodulatory properties. It has been shown that CEACAM1 recruits SHP-1 to the TCR/CD3 complex resulting in reduced phosphorylation of CD3-zeta and ZAP-70 and consequently decreased activation of the ZAP-70 pathway in vitro [5] . CEACAM1 was also shown to modulate T cell activation and Th1 differentiation in vivo, while both activating [14, 15] and inhibitory [16, 17] effects have been reported. In addition to regulating the function of T cells, CEACAM1 acts as a critical survival factor for B cells [18] and modulates the cytolytic function of NK cells [19] . The majority of CD8+ T cells in human melanoma samples were reported to be CEACAM1+ [20] and CEACAM1 and TIM-3 are co-expressed on exhausted murine T cells during induction of tolerance [21] . Tumors implanted in CEACAM1 deficient mice exhibited impaired growth rate and mouse anti-CEACAM1 Ab CC1 prevented tumor growth in combination with anti-PD-L1 or anti-TIM-3 mAbs [21] . These data have led to a proposal that CEACAM1 plays a role as an immune checkpoint, similar to PD1, blocking productive anti-tumor responses in vivo [22] .