Generation, Characterization, and Preclinical Studies of a Novel NKG2A-Targeted Antibody BRY805 for Cancer Immunotherapy

Immuno-oncology has revolutionized cancer treatment, with NKG2A emerging as a novel target for immunotherapy. The blockade of NKG2A using the immune checkpoint inhibitor (ICI) monalizumab has been shown to enhance the responses of both NK cells and CD8+ T cells. However, monalizumab has demonstrated...

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Bibliographic Details
Published in:Antibodies (Basel) 2024-11, Vol.13 (4), p.93
Main Authors: Zhou, Yaqiong, Wang, Yiru, Liang, Jinfeng, Qian, Jing, Wu, Zhenhua, Gao, Zhangzhao, Qi, Jian, Zhu, Shanshan, Li, Na, Chen, Yao, Chen, Gang, Nie, Lei, Guo, Tingting, Wang, Haibin
Format: Article
Language:English
Subjects:
Antibodies
Antitumor activity
Apoptosis
Cancer
Cancer immunotherapy
Cancer therapies
CD8 antigen
Cell death
Clinical trials
Cytotoxicity
Effectiveness
Effector cells
Growth factors
Immune checkpoint inhibitors
Immune system
Immunotherapy
Ligands
Lymphocytes
Lymphocytes T
Monoclonal antibodies
NKG2 antigen
PD-L1 protein
Peptides
Proteins
Tumors
Xenotransplantation
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Summary:Immuno-oncology has revolutionized cancer treatment, with NKG2A emerging as a novel target for immunotherapy. The blockade of NKG2A using the immune checkpoint inhibitor (ICI) monalizumab has been shown to enhance the responses of both NK cells and CD8+ T cells. However, monalizumab has demonstrated limited efficacy in in vitro cytotoxic assays and clinical trials. In our study, we discovered and characterized a novel anti-NKG2A antibody, BRY805, which exhibits high specificity for the human CD94/NKG2A heterodimer complex and does not bind to the activating NKG2C receptor. In vitro cytotoxicity assays demonstrated that BRY805 effectively activated NK92 cells and primary NK cells, thereby enhancing the cytotoxic activity of effector cells against cancer cells overexpressing HLA-E, with significantly greater efficacy compared to monalizumab. Furthermore, BRY805 exhibited synergistic antitumor activity when combined with PD-L1 monoclonal antibodies. In a mouse xenograft model, BRY805 showed superior tumor control relative to monalizumab and demonstrated a favorable safety profile in non-human primate studies.
ISSN:2073-4468
2073-4468
DOI:10.3390/antib13040093