Researcher ORCID Identifier

0009-0002-0616-7541

Graduation Year

2025

Document Type

Campus Only Senior Thesis

Degree Name

Bachelor of Arts

Department

Biology

Reader 1

David Sanford

Reader 2

Emily Wiley

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Terms of Use for work posted in Scholarship@Claremont.

Abstract

Antibody-drug conjugates are a subset of cancer immunotherapy that allows for reduction of harmful side effects by targeting cytotoxic drugs to tumor cells through selective binding. This study focused on anti-CTLA-4-6325, an antibody-drug conjugate that targets tumor stromal cells in sarcomas and carcinomas. Anti-CTLA-4 and 6325 work together to enhance the innate anti-tumor immune response by stimulating and activating inactive T-cells. However, conjugation of 6325 can render the conjugate ineffective by binding to the CTLA-4 and FcɣRIV binding sites, which are essential to the proper function of anti-CTLA-4. In this study, a version of anti-CTLA-4-6325 was created that was blocked from binding to both the CTLA-4 and FcɣRIV binding sites to study the effect of 6325 conjugation on FcɣRIV binding. Protection at the FcɣRIV binding site did not significantly increase the FcɣRIV binding affinity of the conjugate. This was validated through molecular modeling, showing very few available conjugation sites at or near the binding site. Further studies would be needed to further clarify the effects of 6325 conjugation on FcɣRIV binding and anti-CTLA-4 function.

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