NDLI: Development and Characterization of an Anti-Cancer Monoclonal Antibody for Treatment of Human Carcinomas

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Development and Characterization of an Anti-Cancer Monoclonal Antibody for Treatment of Human Carcinomas

Content Provider	MDPI
Author	Tsang, Kwong Yok Fantini, Massimo Mavroukakis, Sharon A. Zaki, Anjum Annunziata, Christina M. Arlen, Philip M.
Copyright Year	2022
Description	NEO-201 is an IgG1 humanized monoclonal antibody (mAb) that binds to tumor-associated variants of carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-5 and CEACAM-6. NEO-201 reacts to colon, ovarian, pancreatic, non-small cell lung, head and neck, cervical, uterine and breast cancers, but is not reactive against most normal tissues. NEO-201 can kill tumor cells via antibody-dependent cell-mediated cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) to directly kill tumor cells expressing its target. We explored indirect mechanisms of its action that may enhance immune tumor killing. NEO-201 can block the interaction between CEACAM-5 expressed on tumor cells and CEACAM-1 expressed on natural killer (NK) cells to reverse CEACAM-1-dependent inhibition of NK cytotoxicity. Previous studies have demonstrated safety/tolerability in non-human primates, and in a first in human phase 1 clinical trial at the National Cancer Institute (NCI). In addition, preclinical studies have demonstrated that NEO-201 can bind to human regulatory T (Treg) cells. The specificity of NEO-201 in recognizing suppressive Treg cells provides the basis for combination cancer immunotherapy with checkpoint inhibitors targeting the PD-1/PD-L1 pathway.
Starting Page	3037
e-ISSN	20726694
DOI	10.3390/cancers14133037
Journal	Cancers
Issue Number	13
Volume Number	14
Language	English
Publisher	MDPI
Publisher Date	2022-06-21
Access Restriction	Open
Subject Keyword	Cancers Oncology Neo-201 Monoclonal Antibody Tumor-associated Antigen Antibody-dependent Cellular Cytotoxicity Complement-dependent Cytotoxicity Natural Killer Cells
Content Type	Text
Resource Type	Article

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