Site‐Selective Tyrosine Reaction for Antibody‐Cell Conjugation and Targeted Immunotherapy
Abstract: Targeted immunotherapies capitalize on the exceptional binding capabilities of antibodies to stimulate a host response that effectuates long‐lived tumor destruction. One example is the conjugation of immunoglobulins (IgGs) to immune effector cells, which equips the cells with the ability to recognize and accurately kill malignant cells through a process called antibody‐dependent cellular cytotoxicity (ADCC). In this study, a chemoenzymatic reaction is developed that specifically functionalizes a single tyrosine (Tyr, Y) residue, Y296, in the Fc domain of therapeutic IgGs. A one‐pot reaction that combines the tyrosinase‐catalyzed oxidation of tyrosine to o‐quinone with a subsequent [3+2] photoaddition with vinyl ether is employed. This reaction installs fluorescent molecules or bioorthogonal groups at Y296 of IgGs or the C‐terminal Y‐tag of an engineered nanobody. The Tyr‐specific reaction is utilized in constructing monofunctionalized antibody‐drug conjugates (ADCs) and antibody/nanobody‐conjugated effector cells, such as natural killer cells or macrophages. These results demonstrate the potential of site‐selective antibody reactions for enhancing targeted cancer immunotherapy.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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Site‐Selective Tyrosine Reaction for Antibody‐Cell Conjugation and Targeted Immunotherapy ; day:03 ; month:12 ; year:2023 ; extent:11
Advanced science ; (03.12.2023) (gesamt 11)
- Urheber
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Chen, Hongfei
Wong, Hong‐Chai Fabio
Qiu, Jiaming
Li, Biquan
Yuan, Dingdong
Kong, Hao
Bao, Yishu
Zhang, Yu
Xu, Zhiyi
Tse, Ying‐Lung Steve
Xia, Jiang
- DOI
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10.1002/advs.202305012
- URN
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urn:nbn:de:101:1-2023120414374954203331
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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23.09.2029, 11:57 MESZ
Datenpartner
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Beteiligte
- Chen, Hongfei
- Wong, Hong‐Chai Fabio
- Qiu, Jiaming
- Li, Biquan
- Yuan, Dingdong
- Kong, Hao
- Bao, Yishu
- Zhang, Yu
- Xu, Zhiyi
- Tse, Ying‐Lung Steve
- Xia, Jiang