# The roles of EBV-specific T cells in response to checkpoint blockade immunotherapy of EBV-driven nasopharyngeal carcinoma

> **NIH NIH R01** · FRED HUTCHINSON CANCER CENTER · 2022 · $603,444

## Abstract

Project Summary/Abstract
Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-driven malignancy that is endemic to East and
Southeast Asia. The overall 5-year survival rate for endemic NPC is only 51%, which represents an unmet clinical
need. While NPC tumors are known to be infected with EBV and express PD-L1, little is known about the role of
EBV-specific T cells in the control of NPC and anti-PD-1 therapy has shown a low rate of efficacy (ORR ~20%).
The goal of this study is to better understand the role of EBV-specific T cell responses in NPC immunopathology
and immunotherapeutic response. We will test the specific hypotheses that: 1. EBV-specific T cells contribute to
tumor control elicited by combination anti-PD-1 and anti-CTLA-4 checkpoint blockade immunotherapy, and 2.
that the phenotypic and clonal characteristics/dynamics of peripheral EBV-specific T cells can be useful as
indicators of clinical outcomes for NPC patients. To test these hypotheses, we will leverage our access to two
Singaporean NPC patient cohorts: Cohort 1. A 51-patient cohort of new-diagnosis NPC for which viably frozen
PBMCs and archival FFPE tissues are available and Cohort 2. A 50-patient cohort participating in a phase II
trial (NCT03097939 - National Cancer Centre Singapore) testing the combination of Ipilumimab and
Nivolumimab (Ipi.+Nivo.) immunotherapy with longitudinally collected PBMCs and tissue biopsies. Recently
published preliminary analysis (AACR 2020) from this clinical trial shows that combined Ipi.+Nivo. therapy is safe
and achieved durable responses in recurrent and metastatic NPC patients and identified a negative association
between circulating EBV-DNA levels and response. In addition, preliminary analysis of new-diagnosis NPC
patient peripheral blood samples from Cohort 1 show associations between certain phenotypic profiles of CD8+
T cells and clinical parameters such as EBV-DNA levels. Therefore, in Aim 1. we will investigate the clinical
relevance of these preliminarily identified NPC-associated CD8+ T cell phenotypes. In addition to in-depth single
cell transcriptional, functional TCR sequence profiling of these cells, cellular imaging, transcriptional profiling and
bulk TCR sequencing of patient-matched tumor will allow discovery of novel associations between peripheral T
cells and the tumor microenvironment. In Aim 2., we will characterize EBV-specific T cell responses in the NPC
periphery and tumor microenvironment during combination Ipi.+Nivo. immunotherapy treatment to identify novel
associations between the phenotypic profiles of EBV-specific T cells and immunotherapeutic response. In Aim
3., we will investigate T cell clonal dynamics associated with treatment induced changes to the NPC-specific
immune response by comparing the TCR clonal diversity in peripheral blood and tumor biopsy samples from
different stages of treatment. Overall, characterization of EBV-specific T cells phenotypes in the NPC periphery
and the tumor using m...

## Key facts

- **NIH application ID:** 10457484
- **Project number:** 5R01CA264646-03
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Evan Newell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $603,444
- **Award type:** 5
- **Project period:** 2021-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10457484

## Citation

> US National Institutes of Health, RePORTER application 10457484, The roles of EBV-specific T cells in response to checkpoint blockade immunotherapy of EBV-driven nasopharyngeal carcinoma (5R01CA264646-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10457484. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*