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Journal of Undergraduate Research

Keywords

chimeric antigen receptor T cells, cancer treatment, CAR T cells

College

Life Sciences

Department

Microbiology and Molecular Biology

Abstract

Cancer negatively affects the lives of millions of individuals, and remains a difficult ailment to treat. In 2014, approximately 585,720 deaths and 1,665,540 new cases of cancer were reported in the USA alone.1 Treatment of cancer is challenging due to cancer mutating to combat the body’s immune system. An example is shown in major histocompatibility complexes (MHCs) located on the surface of nearly every cell. These are patrolled by T cells to ensure that cells are properly functioning and healthy. With cancer however, these become downregulated allowing the cancer to grow and proliferate since T cells are unable to detect them. Chimeric antigen receptor T cells (CAR T cells) overcome this by bypassing the use of MHCs and allowing specific targeting and destruction of cancer cells based on a surface epitope. Recently, CAR T cells targeting B cell cancers have resulted in cancer recession or removal, but overall have had limitations to the extent of cancers treatable.2 This is due to the same epitopes being expressed on both cancer cells and normal, healthy cells, resulting in both cell’s destruction. However, an epitope has been found by the Dr. Kim O’Neill which is highly overexpressed on many types of cancers, allowing T cells to target the malignant cells only. In collaboration with the O’Neill lab, we have begun generating a CAR T cell that specifically targets this epitope. This process has involved sequencing of antibodies that target the epitope; creating a single chain fragment variable (scFv), which links the heavy and light chains of an antibody; and placing this into a T cell. For this project, the sequencing and creation of the scFv was performed.

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