# Allogeneic virus-specific T-cell therapy after hematopoietic stem cell transplant: determinants of treatment success and failure

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2024 · $676,499

## Abstract

ABSTRACT:
Infections caused by double stranded DNA viruses are a common complication after allogeneic
hematopoietic stem cell transplantation (HSCT), occurring in 82% of patients undergoing
transplant at our institution. These infections are a significant source of both morbidity and
mortality in the post-HSCT setting. Commercially available anti-viral medications have
inadequate response rates, prolong hospitalizations, and have narrow therapeutic indexes with
high toxicity rates. Additionally, there are no effective anti-viral medications for two of the more
common viruses, BK polyomavirus (BKPyV) and adenovirus. An alternative approach for viral
management is the use of virus-specific T-cells (VST); this cellular therapy approach uses
peripheral blood from healthy donors to generate highly expanded and viral directed T-cell
populations given as a simple intravenous infusion. This therapy has shown itself across
multiple clinical trials to be safe and highly effective for the treatment of viremia and invasive
viral disease caused by cytomegalovirus (CMV), Epstein-Barr virus (EBV), BKPyV, and
adenovirus. The generalizability of this therapy has increased through use of partially-HLA
matched, ‘off-the-shelf’ third-party VSTs where a product from a VST bank is chosen for a
patient based off of anti-viral activity of the product and the degree of human leukocyte antigen
(HLA) matching. However, while response rates are excellent (on the order of 70-90%
depending on the virus), treatment failures occur even when a good and rationally chosen
product is given.
In this proposal we aim to improve understanding of the mechanisms underlying treatment
success and failure following VST infusion. We hypothesize that both patient- and virus- specific
factors facilitate the effective response to third-party VSTs and that treatment non-response is
due to definable and non-mutually exclusive defects in one or both of these areas. We will use
pre- and post-infusion samples collected from patients enrolled on an active third-party VST
treatment study to complete these aims. From a recipient perspective, we believe that failure of
VST persistence, inadequate antigen presentation, and failure of initial T-cell expansion can be
detected in patients with poor response. From a viral perspective, we will use epitope mapping
and NGS sequencing of viral genome to explore the role of both non-conservation of antigenic
epitopes and antigen escape. We believe that these experiments will generate generalizable
data on mechanisms behind VST treatment with potential implications for improving the therapy
moving forward.

## Key facts

- **NIH application ID:** 10953958
- **Project number:** 1R01HL169242-01A1
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Jeremy D Rubinstein
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $676,499
- **Award type:** 1
- **Project period:** 2024-08-21 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10953958

## Citation

> US National Institutes of Health, RePORTER application 10953958, Allogeneic virus-specific T-cell therapy after hematopoietic stem cell transplant: determinants of treatment success and failure (1R01HL169242-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10953958. Licensed CC0.

---

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