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Author ORCID Identifier

https://orcid.org/0000-0001-5899-1896

Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Molecular and Cellular Biology

Year Degree Awarded

2019

Month Degree Awarded

September

First Advisor

Barbara A. Osborne

Second Advisor

Sankaran Thayumanavan

Third Advisor

Lisa M. Minter

Fourth Advisor

Scott C. Garman

Subject Categories

Biology | Biotechnology

Abstract

In an ideal chemotherapy, cytotoxic drugs travel through the bloodstream, reach cells all over the body and preferentially kill abnormal cells. Yet, the hydrophilic or lipophilic property of the small-molecule drugs affects their ability to reach cells from the bloodstream. So, only a small portion of the drug reaches to the diseased tissue. A selective cell killing approach for cancer therapy gained momentum after the realization that cancer cells carry unique set of molecular markers on their cell surface. The development of antibody drug conjugates (ADC) revolutionized the targeted approach for drug delivery. ADCs are composed of cytotoxic agents covalently linked to a monoclonal antibody that can selectively bind to tumor-markers and deliver its payload to tumor cells. So, off-target effect of the cytotoxic agents on the normal tissue can be avoided. Currently there are four FDA approved ADCs on the market. The number of ADCs in the clinical trials increases continuously even if some of them fail in the efficacy studies. The reasons are cited as low payload capacity of the monoclonal antibody as well as the limitations of the linker chemistry. Our goal in this study is to enhance the antibody mediated targeted drug delivery approach by combining our knowledge in both immunology and polymer chemistry for the treatment of T-cell acute lymphoblastic leukemia (T-ALL) in mouse models, we will engineer anti-CD4 conjugated nanogels loaded with cytotoxic molecules that can: i) selectively target CD4+ T lymphocytes in vitro and in vivo, and ii) eradicate both liquid and solid T-ALL tumors in mouse.

DOI

https://doi.org/10.7275/femp-f280

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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