An engineered interleukin-11 decoy cytokine as a cancer therapeutic
Abstract/Contents
- Abstract
- Cytokines are key signaling molecules in the body and can be exploited by cancer to drive unregulated growth. Chapter 1 focuses on the role of engineered cytokines as therapeutics and their benefits and drawbacks compared to more traditional antibody therapeutics. Chapter 2 focuses on the interleukin (IL)-6 family cytokine, IL-11, which has been shown to be highly expressed in lung adenocarcinoma among other cancer types. As the main goal of this thesis, an engineered high affinity IL-11 antagonist was developed using yeast surface display and directed evolution. This IL-11 variant binds with high affinity to human and mouse IL-11 receptor while lacking binding to the signaling co-receptor gp130. Furthermore, the engineered IL-11 variant potently blocks downstream phospho-STAT3 signaling in cancer cells and significantly reduced tumor growth in a xenograft mouse model of lung cancer. Chapter 3 describes additional efforts to develop a cross-reactive IL-11 antibody that could be developed as a parallel therapeutic approach to the engineered IL-11 cytokine. This antibody work provides a starting point for further antibody campaigns against IL-11 and highlights some of the benefits that engineering cytokines have over antibodies.
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 | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | McIntosh, Brianna |
|---|---|
| Degree supervisor | Cochran, Jennifer R |
| Thesis advisor | Cochran, Jennifer R |
| Thesis advisor | Jackson, Peter K. (Peter Kent) |
| Thesis advisor | Kim, Peter, 1958- |
| Thesis advisor | Sage, Julien |
| Degree committee member | Jackson, Peter K. (Peter Kent) |
| Degree committee member | Kim, Peter, 1958- |
| Degree committee member | Sage, Julien |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Cancer Biology Program |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Brianna Jin-Sun McIntosh. |
|---|---|
| Note | Submitted to the Cancer Biology Program. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/sh448gc2188 |
Access conditions
- Copyright
- © 2023 by Brianna McIntosh
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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