作者
Daniel V Kalinovsky, Alexey V Kibardin, Irina V Kholodenko, Elena V Svirshchevskaya, Igor I Doronin, Mariya V Konovalova, Maria V Grechikhina, Fedor N Rozov, Sergey S Larin, Sergey M Deyev, Roman V Kholodenko
发表日期
2022
期刊
Journal for ImmunoTherapy of Cancer
卷号
10
期号
6
出版商
BMJ Publishing Group
简介
Background
Both ganglioside GD2-targeted immunotherapy and antibody-drug conjugates (ADCs) have demonstrated clinical success as solid tumor therapies in recent years, yet no research has been carried out to develop anti-GD2 ADCs against solid tumors. This is the first study to analyze cytotoxic activity of clinically relevant anti-GD2 ADCs in a wide panel of cell lines with varying GD2 expression and their effects in mouse models of GD2-positive solid cancer.
Methods
Anti-GD2 ADCs were generated based on the GD2-specific antibody ch14. 18 approved for the treatment of neuroblastoma and commonly used drugs monomethyl auristatin E (MMAE) or F (MMAF), conjugated via a cleavable linker by thiol-maleimide chemistry. The antibody was produced in a mammalian expression system, and its specific binding to GD2 was analyzed. Antigen-binding properties and biodistribution of the ADCs in mice were …
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DV Kalinovsky, AV Kibardin, IV Kholodenko… - Journal for ImmunoTherapy of Cancer, 2022