# Adoptive T Lymphocyte Administration for Chronic Norovirus Treatment Following Hematopoietic Stem Cell Transplantation

> **NIH NIH R01** · CHILDREN'S RESEARCH INSTITUTE · 2021 · $722,458

## Abstract

Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for many patients with malignancies
as well as other life-threatening conditions such as primary immunodeficiency disorders (PID). Chronic
norovirus infection is a potential complication of HSCT, and can cause chronic diarrhea and wasting. There are
currently no available therapies to treat norovirus. We have demonstrated that healthy individuals have T cell
immunity against norovirus, and that viral epitopes in antigens NS6 and VP1 are well conserved across viral
genotypes. The overarching goal of this proposal is the development of a novel treatment for chronic norovirus
infection in patients undergoing HSCT. In our previous study, we demonstrated safety and potential efficacy of
virus-specific T cells targeting CMV, EBV, and adenovirus as well as the feasibility of this approach. To restore
immunity against norovirus we now propose to take blood from the healthy donors and expand and enrich the
norovirus-specific T cells (NSTs) present in donors' blood, followed by extensive characterization of the
function of NSTs. We will then give NSTs as treatment for chronic norovirus in patients who have undergone
HSCT. If successful, this novel antiviral therapy could provide long-term protection against norovirus. Thus, we
hypothesize that the infusion of NSTs will be safe and effective against norovirus infections in patients post
HSCT, and will restore lasting immunity against norovirus. We further hypothesize that antiviral efficacy will
correlate with expansion of T cells recognizing immunodominant viral epitopes, which will correspond to stable
regions of the viral genome. Through this phase I IND study, we will address the following specific aims: 1) To
determine the breadth of norovirus T cell epitopes and MHC restrictions, as well as their genetic stability in
clinical viral isolates, 2) To study the safety and feasibility of administering ex vivo expanded T cells targeting
norovirus as treatment of chronic infection in immunocompromised patients, and 3) To determine whether
infusion of NSTs can enhance norovirus specific immunity in immune compromised hosts. Collectively, these
aims will determine if NSTs may be a safe and effective treatment for chronic norovirus infection in patients
post HSCT. Completion of this study could provide a novel antiviral therapy which could reduce virus-
associated morbidity in HSCT, and will guide future cellular therapy and vaccine trials targeting enteric viruses.

## Key facts

- **NIH application ID:** 10149397
- **Project number:** 5R01HL152161-02
- **Recipient organization:** CHILDREN'S RESEARCH INSTITUTE
- **Principal Investigator:** Michael Daniel Keller
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $722,458
- **Award type:** 5
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10149397

## Citation

> US National Institutes of Health, RePORTER application 10149397, Adoptive T Lymphocyte Administration for Chronic Norovirus Treatment Following Hematopoietic Stem Cell Transplantation (5R01HL152161-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10149397. Licensed CC0.

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