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 assess whether intratumoral immune activation is altered following monotherapy or combination treatment with CC1 and muDX400, tumor infiltrates were isolated from the CT26 model. Multiple parameters were analyzed: absolute numbers of CD8+ and Treg cells, ratio between CD8+ and Treg cells, and the frequency of ICOS+ CD8+ T cells in CT26 tumor at day 8 post initial dosing of each group. No significant increase in numbers of CD8+ T cells or Treg cells were found in the tumors of mice treated with muDX400, CC1 or the combination ( Figure 6A and 6B) . There was no effect of treatment on CD8+ T cells/Treg ratios ( Figure 6C ). In previous studies, it has been demonstrated that one of the co-stimulatory receptors, inducible co-stimulator (ICOS) is expressed on CD8+ T cells when an immune check point blockade is effective [26] . For a qualitative assessment of intratumoral CD8 T cells after each treatment, the frequency of ICOS-expressing CD8 T cells was monitored. muDX400 monotherapy group showed a significant expansion of ICOS+ CD8 T cells in CT26 tumors, compared to those in the isotype control group. CC1 did not significantly increase ICOS expression as a monotherapy or when combined with muDX400 ( Figure 6D ). In addition, no consistent changes in the proportions of CD4+, NK cells, B cells, monocytes, dendritic cells or myeloid-derived suppressor cells (myeloid or granulocytic) upon CC1 treatment were observed (data not shown).