# Glycoengineering of antibodies to modulate immune functions

> **NIH NIH R01** · UNIV OF MARYLAND, COLLEGE PARK · 2020 · $662,880

## Abstract

Project Summary
Antibodies are an important class of therapeutics that are widely used for treatment of cancer, autoimmune
diseases, and infectious diseases. Compelling experimental data have demonstrated that Fc glycosylation is a
critical structural determinant for modulating antibody’s effector functions, including antibody-dependent
cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), activation of apoptosis, and anti-
inflammatory activities. However, progress in understanding the functional roles of antibody glycosylation is
hampered by the tremendous structural heterogeneity of Fc glycosylation. To address this problem, we have
developed a chemoenzymatic method that permits site-specific Fc and Fab glycan remodeling to generate
homogeneous antibody glycoforms. In ths application, we propose to exploit the site-specific chemoenzymatic
glycan remodeling method as a key platform technology to address three important questions related to
antibody functions, as highlighted in the following three specific aims. Aim 1 is to understand how Fc
glycosylation modulate Fc receptor binding and ADCC activity by selective modification of the core fucose, by
performing structural studies, and by synthesizing novel glycoforms, coupled with Fc receptor binding and
ADCC assays. Aim 2 is to evaluate how site-specific sialylation of Fc glycans affects antibody’s anti-
inflammatory activity by constructing asymmetrically sialylated or multiply sialylated glycoforms, coupled with
animal studies. Aim 3 is to augment antibody’s complement-dependent cytotoxicity (CDC) by constructing
structurally well-defined Gal/rhamnose antigen-antibody conjugates to recruit natural IgG and IgM antibodies
in circulation. These studies will yield important new knowledge in glyco-immunology, which will facilitate the
development of more effective antibody-based therapeutics.

## Key facts

- **NIH application ID:** 10099594
- **Project number:** 1R01AI155716-01
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** LAI-XI WANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $662,880
- **Award type:** 1
- **Project period:** 2020-09-17 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10099594

## Citation

> US National Institutes of Health, RePORTER application 10099594, Glycoengineering of antibodies to modulate immune functions (1R01AI155716-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10099594. Licensed CC0.

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