RT Journal Article
SR Electronic
T1 Discovery and pre-clinical evaluation of antibodies to the NKG2A inhibitory receptor
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.05.18.492494
DO 10.1101/2022.05.18.492494
A1 Du-San Baek
A1 Ye-Jin Kim
A1 Wei Li
A1 Bernard JC Macatangay
A1 Joshua C. Cyktor
A1 Margaret G. Hines
A1 John W. Mellors
A1 Dimiter S. Dimitrov
YR 2022
UL http://biorxiv.org/content/early/2022/05/19/2022.05.18.492494.abstract
AB NK and CD8+ T cells are important cells for cytolysis of cancer cells. The tumor microenvironment can upregulate surface expression on these cells of NKG2A, an inhibitory receptor that can dampen immune responses to cancer leading to immune evasion. To block NKG2A-mediated inhibition, we discovered and characterized two fully human antibodies using phage and yeast display that bind to NKG2A. These antibodies are highly specific for human CD94/NKG2A heterodimer complex, displaying no binding to the activating NKG2C receptor. A mutagenesis study revealed that the serine residue at 170 position (S170) of NKG2A is critical for the selectivity of anti-NKG2A antibodies. In vitro cytotoxic assays showed that NKG2A antibody inhibitors activated primary NK cells and promoted ADCC function of specific antibodies that bind to antigens expressed on cancer cells.Summary heading Fully human antibodies to the NKG2A inhibitory receptorCompeting Interest StatementThe authors have declared no competing interest.