Engineering self-assembling superantigen as cancer immunotherapy
Abstract/Contents
- Abstract
- Superantigens are the most potent immune activating molecules known in nature. As such, they hold unique potential in the field of cancer immunotherapy, where treatments demand vigorous stimulation of the immune system. Studies in immunotherapy point to a tension between two opposing factors: the need to increase effectiveness while decreasing adverse reactions. Superantigens provide an avenue for a magnified boosting of the immune system, but likewise necessitate greater molecular control and precision to leverage this capacity. This thesis focuses on utilizing computational tools to propose a novel method for introducing molecular logic gate control into an existing superantigen, and consequently harness the unique ability of these proteins while providing a mechanism for control. In the first chapter, we begin with a review of the molecular interactions and strategies behind existing superantigen therapies. We then leverage the computational protein design program RosettaRemodel in chapter two in order to design the molecular logic gates AND and NOT into a superantigen through creating a novel fusion protein between the Mycoplasma Arthritidis Mitogen superantigen and the TIM (triose-phosphate isomerase) barrel. Next, in chapter three we express a focused library of computational solutions and identify the optimal conditions for production and characterization of an ideal design. Finally, in chapter four we experimentally test and quantify the anti-tumor activity of our designed superantigen through both in vitro and in vivo studies, ending with conclusion of our work in chapter five.
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 | Parra Sperberg, Ricardo Andres |
|---|---|
| Degree supervisor | Cochran, Jennifer R |
| Degree supervisor | Huang, Possu |
| Thesis advisor | Cochran, Jennifer R |
| Thesis advisor | Huang, Possu |
| Thesis advisor | Engleman, Edgar G |
| Degree committee member | Engleman, Edgar G |
| Associated with | Stanford University, School of Engineering |
| Associated with | Stanford University, Department of Bioengineering |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | R. Andres Parra Sperberg. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis Ph.D. Stanford University 2024. |
| Location | https://purl.stanford.edu/kj672fq2413 |
Access conditions
- Copyright
- © 2024 by Ricardo Andres Parra Sperberg
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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