Engineered proteins to NKp46 for cancer therapeutics
Abstract/Contents
- Abstract
- NKp46 (NCR1, CD335) is an activating receptor expressed on the surface of natural killer (NK) cells in the immune system. NKp46 has been the target of NK cell engaging bispecific antibodies in recent years, with multiple studies demonstrating the potential of engaging NKp46 for antitumor responses in cancer. In this thesis, I discuss the discovery and engineering of antibodies and fibronectin domain proteins that bind to either human NKp46, mouse NKp46, or both using phage display and yeast surface display. One species cross-reactive antibody was epitope mapped to conserved mouse and human amino acid residues and could induce NK cell proliferation and activation. A panel of NK cell engager (NKCE) bispecific antibody constructs was created from binders of both NKp46 and the tumor antigen CD20 to explore NCKE configurations, valency, and Fc effector functions. NKp46 engagement with the bispecific antibodies was shown to increase NK cell cytotoxicity against tumor cells as compared to the anti-CD20 antibody alone in an Fc-independent manner. This thesis contributes to a body of work related to NKp46, NCKEs, and cancer therapeutics, and provides a number of proteins as useful tools for basic science and translational applications.
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 | 2024; ©2024 |
| Publication date | 2024; 2024 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Lee, Robert Benjamin |
|---|---|
| Degree supervisor | Cochran, Jennifer R |
| Degree supervisor | Swartz, James R |
| Thesis advisor | Cochran, Jennifer R |
| Thesis advisor | Swartz, James R |
| Thesis advisor | Sunwoo, John B |
| Degree committee member | Sunwoo, John B |
| Associated with | Stanford University, School of Engineering |
| Associated with | Stanford University, Department of Chemical Engineering |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Robert Benjamin Lee. |
|---|---|
| Note | Submitted to the Department of Chemical Engineering. |
| Thesis | Thesis Ph.D. Stanford University 2024. |
| Location | https://purl.stanford.edu/vd690jd0116 |
Access conditions
- Copyright
- © 2024 by Robert Benjamin Lee
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