Date of Award

Spring 2013

Document Type

Restricted Thesis

Terms of Use

© 2013 Erin Murphy Curtis. All rights reserved. Access to this work is restricted to users within the Swarthmore College network and may only be used for non-commercial, educational, and research purposes. Sharing with users outside of the Swarthmore College network is expressly prohibited. For all other uses, including reproduction and distribution, please contact the copyright holder.

Degree Name

Bachelor of Arts

Department

Biology Department

First Advisor

Amy Cheng Vollmer

Abstract

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer-related death in women in the U. S. and the most lethal of gynecological malignancies. Current standard treatment often achieves a period of remission during which specific antigen-targeted vaccine treatment could be effective. Immunogenic potential exists for subdominant epitopes of self-proteins upregulated in EOC patients. Candidate proteins based on overexpression and associate with poor prognosis in EOC were evaluated for peripheral blood mononuclear cells (PBMC) responses through IFN-γ and IL-I0 ELISpots. ELISpots indicated significantly higher IFN-γ responses to MMP-2 and BRCAI p42-59; IL-I0 responses were marginally higher for Claudin-3. Percent incidence of positive responses in IFN-γ assays was high in cancer patients for BRCAI p42-59, Claudin3, and AuroraAR kinase. These results begin to elucidate the immunogenicity of these peptides and suggest a potential role for the development of a peptide-based vaccine for ovarian cancer. EOC remains poorly understood, largely because animal models that realistically mimic the human disease have eluded scientists. We also describe a syngeneic, immunocompetent mouse model using mouse ovarian surface epithelial cells (MOSEC) expressing codon-optimized luciferase for the evaluation of immunotherapies for ovarian cancer. Transformed MOSEC were transduced with lentivirus expressing codon-optimized luciferase. Clones were selected, expanded and screened for luminescence. Tumor cells were injected intraperitoneally, and external measures of tumor growth and luminescence were observed. Significant increase in weight was seen only after 6 weeks, whereas luminescence was detected after 2 weeks. Luminescence doubled every two weeks until week 6 and reached 9700 U at week 8. Serum antibody response to luciferase was minimal. Immunohistochemistry showed extensive, heterogeneous infiltration of CD3 T-cells. Overall, this study identifies antigens for the development of a peptide-based vaccine for ovarian cancer and describes an effective model for the evaluation of this vaccine and other novel immunotherapies for ovarian cancer that allows for in vivo monitoring of minimal tumor growth and maintains important tumor-host relationship analogous to human disease.

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