Dissertation
Effect of polymer chemistry in polymeric microparticle based cancer vaccines
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Summer 2021
DOI: 10.17077/etd.005937
Abstract
Cancer is a deadly disease that is caused by cells growing uncontrollably and leads to death due to the burden it puts on the body. Cancer is the second highest causes of death in the United States despite current treatments and preventive measures taken by patients and doctors. Due to the current high number of cancer cases, there is more interest in developing cancer vaccines. Polymeric microparticles are a delivery system of interest in cancer vaccines as a method to deliver antigens. In this work we aim to study the effect polymers have in cancer vaccines based on the chemical structure of the polymers affecting hydrophobicity. In our first investigation of the effect polymers have in cancer vaccines based on chemical structure we looked at two heterologous prime-boost vaccines loaded with ovalbumin. The two polymers of interest were 50:50 poly(lactic-co-glycolic) acid and 75:25 poly(lactic-co-glycolic) acid. Heterologous prime-boost vaccines are used to promote a higher immune response than homologous prime-boost vaccines. A heterologous prime-boost vaccine was used in a murine study. The prime was composed of ovalbumin, a model antigen, encapsulated in poly(lactic-co-glycolic) acid polymer. Attenuated adenovirus encoding for ovalbumin was the boost. The microparticle formulation extends exposure of the antigen by releasing the encapsulated antigen for a prolonged period of time. Hydrophobicity of the polymer used resulted in an altered particle hydrophobicity and encapsulation of the antigen resulting in different release rates, solubility, and efficacy of the cancer vaccine. Studies were performed to determine the optimal microparticle formulation made with 50:50 poly(lactic-co-glycolic) acid or 75:25 poly(lactic-co-glycolic) acid in a heterologous prime-boost cancer vaccine. We found that a more hydrophilic microparticle formulation made with 75:25 poly(lactic-co-glycolic) acid is more effective in a heterologous prime-boost cancer vaccine.
In our second investigation we looked at the efficacy of an immunostimulatory polymer, poly(4,4’-trimethylenedipiiperdyl sulfide), in a cancer vaccine. Additionally, use of poly(4,4’-trimethylenedipiiperdyl sulfide) as a delivery system in a cancer vaccine was compared to polylactic acid polymer. Ovalbumin was encapsulated in both poly(4,4’-trimethylenedipiiperdyl sulfide) and polylactic acid polymers. Efficacy of the tumor vaccine was determined by dosing mice with the vaccine, challenging mice with E.g7 tumors, then measuring survival. Mice treated with poly(4,4’-trimethylenedipiiperdyl sulfide) ovalbumin loaded particles showed 90% survival and the highest cancer vaccine efficacy.
Details
- Title: Subtitle
- Effect of polymer chemistry in polymeric microparticle based cancer vaccines
- Creators
- Alexis Annette Ellis
- Contributors
- Aliasger K Salem (Advisor)Mark A Arnold (Committee Member)Johna Leddy (Committee Member)Maxwell L Geng (Committee Member)Ned B Bowden (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Chemistry
- Date degree season
- Summer 2021
- DOI
- 10.17077/etd.005937
- Publisher
- University of Iowa
- Number of pages
- xii, 56 pages
- Copyright
- Copyright 2021 Alexis Annette Ellis
- Language
- English
- Description illustrations
- color illustrations
- Description bibliographic
- Includes bibliographical references (pages 54-56).
- Public Abstract (ETD)
Cancer is the number two cause of death in the United States. Current treatments are surgery, chemotherapy, radiology, and immunotherapy. Immunotherapy is a relatively new treatment in the fight against cancer that trains a person’s immune system to fight against cancer cells. One way a person’s immune system can be trained to fight against cancer cells is by giving the person a cancer vaccine. The vaccine contains, or encodes for, a protein (antigen) that is specific or associated with the cancer which the immune system learns to recognize as foreign and attempts to eliminate it. Through this process a person’s immune system can learn to fight against cancer cells.
In our work we looked at the effect delivery systems for the antigens have on the efficacy of cancer vaccines. Length of time of exposure of the immune system to the antigens affects the efficacy of the vaccine. Therefore, we investigated delivery systems of different chemical compositions that increased or decreased the time the antigen was exposed to the immune system. Results showed that systems allowing for longer exposure increased the anti-cancer response.
- Academic Unit
- Craniofacial Anomalies Research Center; Chemistry
- Record Identifier
- 9984124359202771
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