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Synthetic Antibody-Rhamnose Cluster Conjugates Show Potent Complement-Dependent Cell Killing by Recruiting Natural Antibodies.


ABSTRACT: Monoclonal antibodies (mAbs) are one of the most rapidly growing drug classes used for the treatment of cancer, infectious and autoimmune diseases. Complement-dependent cytotoxicity (CDC) is one of the effector functions for antibodies to deplete target cells. We report here an efficient chemoenzymatic synthesis of structurally well-defined conjugates of a monoclonal antibody with a rhamnose- and an αGal trisaccharide-cluster to recruit natural anti-rhamnose and anti-αGal antibodies, respectively, to enhance the CDC-dependent targeted cell killing. The synthesis was achieved by using a modular antibody Fc-glycan remodeling method that includes site-specific chemoenzymatic Fc-glycan functionalization and subsequent click conjugation of synthetic rhamnose- and αGal trisaccharide-cluster to provide the respective homogeneous antibody conjugates. Cell-based assays indicated that the antibody-rhamnose cluster conjugates could mediate potent CDC activity for targeted cancer cell killing and showed much more potent efficacy than the antibody-αGal trisaccharide cluster conjugates for CDC effects.

SUBMITTER: Ou C 

PROVIDER: S-EPMC8930617 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Synthetic Antibody-Rhamnose Cluster Conjugates Show Potent Complement-Dependent Cell Killing by Recruiting Natural Antibodies.

Ou Chong C   Prabhu Sunaina Kiran SK   Zhang Xiao X   Zong Guanghui G   Yang Qiang Q   Wang Lai-Xi LX  

Chemistry (Weinheim an der Bergstrasse, Germany) 20220221 16


Monoclonal antibodies (mAbs) are one of the most rapidly growing drug classes used for the treatment of cancer, infectious and autoimmune diseases. Complement-dependent cytotoxicity (CDC) is one of the effector functions for antibodies to deplete target cells. We report here an efficient chemoenzymatic synthesis of structurally well-defined conjugates of a monoclonal antibody with a rhamnose- and an αGal trisaccharide-cluster to recruit natural anti-rhamnose and anti-αGal antibodies, respectivel  ...[more]

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