Wei, Yuan
(2016)
CO-DELIVERY OF PACLITAXEL AND IMATINIB BY PEG DERIVATIZED NLG CARRIER AS ENHANCED IMMUNOCHEMOTHERAPY.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Indoleamine 2,3-dioxygenase (IDO), which catalyzes the initial and rate-limiting step in the tryptophan catabolism along the kynurenine pathway, is an immunosuppressive enzyme that can lead to T cell anergy, apoptosis and potential induction of regulatory T cells (Treg cells). This discovery has led to the development of several IDO inhibitors including NLG919, an immunotherapy drug that targets IDO with high efficacy, into the clinical trial for treating solid tumor. Our goal is to develop PEG derivatized NLG as a functional carrier for specifically delivering anticancer agents to the tumor site to stimulate immune response and eliminate systemic toxicity. Previously, our group has developed a PEG2K-Fmoc-NLG micellar system that can effectively deliver anticancer drug Paclitaxel (PTX) and synergize with chemotherapy to reduce tumor growth. One major limitation with this approach is the feedback mechanism following NLG-mediated inhibition of IDO, which subsequently leads to the up-regulation of IDO expression. In addition, the mRNA expression of IDO can be further enhanced by PTX treatment. For long-term treatment, increased dose of this formulation would be necessary to maintain the same effect for treating cancer. The focus of our study is to identify a compound that can effectively inhibit the expression of IDO at transcriptional level and develop an improved PEG-NLG-based carrier for codelivery of the compound and a chemotherapeutic agent such as PTX.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
29 July 2016 |
| Defense Date: |
17 May 2016 |
| Approval Date: |
9 August 2016 |
| Submission Date: |
1 August 2016 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
41 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Pharmacy > Pharmaceutical Sciences |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
No |
| Uncontrolled Keywords: |
co-delivery, ido, immunotherapy, immunochemotherapy |
| Article Type: |
Research Article |
| Date Deposited: |
09 Aug 2016 14:34 |
| Last Modified: |
15 Nov 2016 14:35 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/29062 |
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