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

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Background:

• Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has dual roles in tumor progression and suppression.
• CEACAM1 signaling blockade is a potential cancer immunotherapy strategy.
• The anti-CEACAM1 antibody CC1 is a common preclinical tool, but its blocking characteristics and pharmacokinetics are not well-defined.

Purpose of the Study:

• To investigate CEACAM1 expression on mouse tumor and immune cells.
• To characterize the binding of CC1 mAb to CEACAM1.
• To evaluate CC1 as a monotherapy and in combination with anti-PD-1 in syngeneic mouse cancer models.

Main Methods:

• Flow cytometry to assess CEACAM1 expression on various immune and tumor cells.
• In vitro binding assays to characterize CC1 mAb interaction with CEACAM1.
• In vivo efficacy studies using CT26, MBT2, and A20 mouse cancer models treated with CC1 alone or with anti-PD-1.

Main Results:

• High CEACAM1 expression was found on neutrophils, NK cells, and myeloid-derived suppressor cells (MDSCs); low expression was observed on tumor-infiltrating CD8+ T cells.
• CC1 antibody facilitated soluble CEACAM1 binding to cells, contrary to a blocking mechanism.
• CC1 monotherapy or combination with anti-PD-1 did not yield significant anti-tumor effects in tested models, even at doses achieving high target engagement.

Conclusions:

• Tumor-infiltrating CD8+ T cells express low levels of CEACAM1, limiting the potential efficacy of CEACAM1-targeted therapies in this context.
• The CC1 antibody's mechanism appears to involve CEACAM1 binding facilitation rather than blockade, and it demonstrates minimal to no anti-tumor activity in vivo.
• Further research is needed to explore alternative strategies for targeting the CEACAM1 pathway in cancer immunotherapy.