Engineering reagents to target the sialic acid glyco-immune checkpoint
Abstract/Contents
- Abstract
- Sugar molecules decorate the human cell surface, creating a dense network of glycoproteins, glycolipids, and proteoglycans known as the glycocalyx. One "hallmark" of cancer cells is an overrepresentation of sialic acid-containing sugar structures (sialoglycans) in the glycocalyx. These sialoglycans bind to the "Sialic acid binding Ig-like Lectin" (Siglec) inhibitory receptor family expressed on both innate and adaptive immune cells. Immune inhibitory signaling of sialoglycans is therefore exploited by cancer cells to prevent an antitumor immune response and promote cancer cell survival. Because of this, sialic acids can be considered glyco-immune checkpoint ligands and represent promising therapeutic targets. Blocking sialoglycan interactions with typical antibody reagents is challenging, however, due to their vast chemical diversity; sialic acids are a family of ~50 sugar molecules in humans that can be chemically linked in multiple ways to numerous glycoproteins and glycolipids. In addition, there is a relative scarcity of high-affinity, glycoform-specific antibodies, and the precise structures of the most potent Siglec ligands remain unclear. To address this, this work describes the development of unique biological reagents to block the sialoglycan-Siglec inhibitory checkpoint interaction for cancer therapy.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2021; ©2021 |
| Publication date | 2021; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Gray, Melissa Anne |
|---|---|
| Degree supervisor | Bertozzi, Carolyn R, 1966- |
| Thesis advisor | Bertozzi, Carolyn R, 1966- |
| Thesis advisor | Boxer, Steven G. (Steven George), 1947- |
| Thesis advisor | Cegelski, Lynette |
| Degree committee member | Boxer, Steven G. (Steven George), 1947- |
| Degree committee member | Cegelski, Lynette |
| Associated with | Stanford University, Department of Chemistry |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Melissa A. Gray. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/cc809pt5360 |
Access conditions
- Copyright
- © 2021 by Melissa Anne Gray
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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