"Tcr Modifications to Enhance Expression, Chain Pairing, and Antigen Re" by Kendra Foley

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

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