Abstract 262: Inhibition of the novel immune checkpoint CEACAM1 enhances antitumor immunological activity

• Published in: Cancer research (Chicago, Ill.) Ill.), 2015-08, Vol.75 (15_Supplement), p.262-262
• Main Authors: Markel, Gal, Mandel, Ilana, Sapir, Yair, Hakim, Motti, Hashmueli, Sharon, Ben-Moshe, Tehila
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2015-262

Blockade of co-inhibitory immune receptors has become a promising approach for the activation of anti-tumor immunity. CEACAM1, a recently characterized immune checkpoint, is a member of the Ig superfamily expressed by activated effector lymphocytes and cancer cells. Expression of CEACAM1 on cancer cells induces a co-inhibitory signal to T and NK cells through homophilic CEACAM1 interactions. CEACAM1 is expressed across multiple tumor types and its presence is independent of PD-L1 expression. CM-24 is a humanized anti-CEACAM1 IgG4 antibody with high affinity and selectivity for CEACAM1. We investigated the activity of CM-24 and its ability to reverse CEACAM1-induced immune evasion alone and in combination with other checkpoint inhibitors. CM-24 was demonstrated to be a potent blocker of intercellular CEACAM1-CEACAM1 interactions and reversed inhibition of activated lymphocytes by restoring the phosphorylation signal of ZAP70. CM-24 enhanced the cytotoxic activity of cytotoxic T cell and NK cells against various cancer types, which was accompanied by higher secretion of Granzyme B and IFNγ. In addition, a synergistic activity with various immune checkpoint blockers was observed, including ones that target the PD-1 pathway. Various in vivo tumor xenograft models demonstrated that CM-24 has clear anti-tumor activity accompanied by an increase in immunological activity of T cells within the tumor. Collectively, preclinical data show that CM-24 has effective anti-tumor activity in various in vitro and in vivo models and demonstrate that CM-24 has the potential to enhance the cytotoxic activity of lymphocytes against malignant cells. CM-24 is now moving towards phase 1 clinical study. Citation Format: Gal Markel, Ilana Mandel, Yair Sapir, Motti Hakim, Sharon Hashmueli, Tehila Ben-Moshe. Inhibition of the novel immune checkpoint CEACAM1 enhances antitumor immunological activity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 262. doi:10.1158/1538-7445.AM2015-262