# Role of Antigen Glycosylation in Mucin Binding by Monoclonal Antibodies

> **NIH NIH R15** · CALIFORNIA STATE UNIVERSITY FRESNO · 2020 · $414,854

## Abstract

PROJECT SUMMARY
Immunotherapy has become one of the central pillars of cancer treatment. The deployment of antibody-based
therapies has transformed the lives of thousands of patients. A molecular understanding of how antibodies
interact with their targets is invaluable for the development of new successful antibody drugs and immunotherapy
products. One of the most important targets for the discovery of new cancer immunotherapies is the mucin family
of glycoproteins. Mucin proteins are frequently overexpressed and display altered abnormal glycosylation in
several types of adenocarcimona. However, despite the importance of mucin proteins as immunotherapy
targets, little is known regarding how antibodies bind these proteins. To address this gap in our knowledge, we
propose using a panel of antibodies that bind the mucins MUC1 and MUC16 as models to understand molecular
recognition of these important therapeutic targets. Preliminary studies in our lab have demonstrated that
glycosylation of MUC1 influences the conformational dynamics of epitopes which in turn influence antibody
binding. We will expand our understanding of this phenomenon using a combination of structural biology,
computational modeling and binding studies on a panel of MUC1 specific antibodies. Specifically, we aim to
determine the role of cancer associated mucin glycosylation in antibody recognition of MUC1 (AIM 1). Previously
published results suggest that MUC16 antibodies bind non-linear epitopes localized within the tandem-repeat
region of the protein. This region is heavily glycosylated, and the role of MUC16 glycosylation on antibody
binding is unknown. Preliminary studies in our lab have determined that a humanized MUC16 antibody binds to
an epitope with a SEA domain. Using several therapeutic antibody candidates as models, we propose to employ
structural and binding studies to characterize the nature of non-linear MUC16 epitopes recognized by
therapeutic antibodies (AIM 2).

## Key facts

- **NIH application ID:** 10045898
- **Project number:** 1R15CA242349-01A1
- **Recipient organization:** CALIFORNIA STATE UNIVERSITY FRESNO
- **Principal Investigator:** Cory Brooks
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $414,854
- **Award type:** 1
- **Project period:** 2020-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10045898

## Citation

> US National Institutes of Health, RePORTER application 10045898, Role of Antigen Glycosylation in Mucin Binding by Monoclonal Antibodies (1R15CA242349-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10045898. Licensed CC0.

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