Date of Award

2015

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Microbiology and Immunology

Abstract

T cell receptor (TCR) gene modified T cells for adoptive T cell transfer therapy have been shown to have clinical success in treating melanoma and other malignancies by redirecting the specificity of peripheral blood lymphocytes (PBL) to recognize tumor and/or viral associated antigens of choice. One of the challenges in using TCR gene modified T cells is the potential mispairing between endogenous and introduced alpha and beta TCR chains, allowing for unwanted off-target reactivity, autoimmunity, or impaired therapeutic efficacy. One approach to augment proper TCR chain pairing and to enhance T cell function involves the modification of the introduced TCR genes to promote proper pairing. Our studies have demonstrated that while certain modifications to a HCV NS3:1406-1415-reactive TCR can augment properly paired introduced TCRs expressed on the cell surface, this does not always correlate to increased T cell function. A better understanding of how modifications to TCRs can influence pairing and function will enhance our ability to improve gene-modified T cells for adoptive transfer.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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