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Keywords

Cancer Immunotherapy, Biomarker, Antibody

Abstract

Effective immunotherapeutic targeting of cancer cells requires identification of specific antigenic differences between cancerous and healthy cells. Hypoxanthine-guanine phosphoribosyltransferase (HPRT) is a cytoplasmic enzyme involved in the salvage pathway for DNA synthesis. Certain cancers (e.g., prostate and breast) upregulate and express HPRT on the cell membrane, making HPRT a potential cancer biomarker for cancer immunotherapies. Antibodies specific for unique cancer proteins are critical to develop targeted cancer immunotherapies. Using a yeast display library and cell sorting, we selected for high-affinity human single-chain (scFv) antibodies against HPRT that can be utilized in chimeric antigen receptor (CAR) T cell therapies and antibody-dependent therapeutic approaches. Our initial screening identified a clone that binds to HPRT at a 20 nM concentration. Isolation and characterization of 20 HPRT specific clones for their ability to target cancer cells without destroying healthy cells is the critical next step in this HPRT immunotherapy development. Quantification of binding affinity and specificity will determine the best clones to transfer into an antibody-dependent (ADCC) or chimeric antigen receptor (CAR) T cell construct to evaluate cytotoxicity efficacy.

Document Type

Poster

Publication Date

2023-03-03

Language

English

College

Life Sciences

Department

Biology

University Standing at Time of Publication

Junior

Isolating Highly Specific Antibodies Against Cancer Target HPRT

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Biology Commons

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