Epstein-Barr Virus-positive Nasopharyngeal Carcinoma: Monitoring immune status and developing therapy with TCR-T cells Shweta

This thesis is about Nasopharyngeal carcinoma (NPC) and adoptive T cell therapy (ATC).
ATC involves transfusion of patients with autologous T cells engineered with a T cell
receptor (TCR) or a chimeric antigen receptor (CAR) targeting tumor antigens. In context
of NPC, TCRs targeting Epstein Barr virus (EBV) genes have potential for being candidates
for ATC therapy against recurrent or metastatic NPC (RM-NPC). Chapter 1 introduces this
dissertation and provides an overview of the incidence, diagnosis, and current treatment
of NPC. I also describe the immune microenvironment of NPC and the prominent role of
EBVgenes in NPConcogenesis and immunity. I also introduce the relevance of EBV genes
as targets for immunotherapies such as adoptive T-cell therapy and immunomodulation
to counter immune evasion in patients with RM-NPC.
This dissertation is divided into two parts:
Chapter 7
Part 1 of this dissertation focuses on the identification of novel EBV T-cell receptors (TCRs)
for adoptive T-cell therapy in RM-NPC patients.
Part 2 focuses on the immune microenvironment of NPC and the role of EBV genes in
immuneevasion,Tcellinfiltration, andantigenpresentation. ThispartalsoaddressesEBV
genes as targets for immunomodulation strategies in addition to EBV-TCR T cell therapy.