The Monoclonal Antibody NEO-201 Enhances Natural Killer Cell Cytotoxicity Against Tumor Cells Through Blockade of the Inhibitory CEACAM5/CEACAM1 Immune Checkpoint Pathway | Zendy

Massimo Fantini | Zendy; Justin M. David | Zendy; Christina M. Annunziata | Zendy; Maria Pia Morelli | Zendy; Phillip M. Arlen | Zendy; Kwong Y. Tsang | Zendy

Open Access

The Monoclonal Antibody NEO-201 Enhances Natural Killer Cell Cytotoxicity Against Tumor Cells Through Blockade of the Inhibitory CEACAM5/CEACAM1 Immune Checkpoint Pathway

Author(s) -

Massimo Fantini,

Justin M. David,

Christina M. Annunziata,

Maria Pia Morelli,

Phillip M. Arlen,

Kwong Y. Tsang

Publication year - 2020

Publication title -

cancer biotherapy and radiopharmaceuticals

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.716

H-Index - 59

eISSN - 1557-8852

pISSN - 1084-9785

DOI - 10.1089/cbr.2019.3141

Subject(s) - cytotoxicity , lymphokine activated killer cell , cancer research , nk 92 , biology , antibody , interleukin 21 , interleukin 12 , monoclonal antibody , immune system , cancer cell , innate immune system , natural killer cell , carcinoembryonic antigen , cell culture , cytotoxic t cell , in vitro , immunology , cancer , t cell , biochemistry , genetics

Background: Natural killer (NK) cells are essential to innate immunity and participate in cancer immune surveillance. Heterophilic interactions between carcinoembryonic antigen (CEA) on tumor cells and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) on NK cells inhibit NK cell cytotoxicity against tumor cells. NEO-201 is a humanized IgG1 monoclonal antibody that recognizes members of CEACAM family, expressed specifically on a variety of human carcinoma cell lines and tumor tissues. This investigation was designed to determine whether the binding of NEO-201 with CEACAM5 on tumor cells can block the CEACAM5/CEACAM1 interaction to restore antitumor cytotoxicity of NK cells. Materials and Methods: In vitro functional assays, using various human tumor cell lines as target cells and NK-92 cells as effectors, were conducted to assess the ability of NEO-201 to block the interaction between CEACAM5 on tumor cells and CEACAM1 on NK cells to enhance the in vitro killing of tumor cells by NK-92. NK-92 cells were used as a model of direct NK killing of tumor cells because they lack antibody-dependent cellular cytotoxicity activity. Results: Expression profiling revealed that various human carcinoma cell lines expressed different levels of CEACAM5 + and NEO-201 + cells. Addition of NEO-201 significantly enhanced NK-92 cell cytotoxicity against highly CEACAM5 + /NEO-201 + expressing tumor cells, suggesting that its activity is correlated with the level of CEACAM5 + /NEO-201 + expression. Conclusions: These findings demonstrate that NEO-201 can block the interaction between CEACAM5 on tumor cells and CEACAM1 on NK cells to reverse CEACAM1-dependent inhibition of NK cytotoxicity.

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