# CMV, ADV and EBV Viral Cytotoxic T-Lymphocytes Generated by a Novel Cytokine Capture System in Children,Adolescents and Young Adults with Refractory Viral Infection and T-Cell Immunodeficiency

> **NIH FDA R01** · NEW YORK MEDICAL COLLEGE · 2021 · $425,145

## Abstract

Project Summary
Children, adolescents and young adults (CAYA) with a primary T-cell immunodeficiency (PID) and/or
secondary T-cell immunodeficiency following allogeneic stem cell transplantation (AlloSCT) and a medically
refractory CMV, ADV and/or EBV infection and/or who become intolerant to antiviral antibiotics have a dismal
prognosis (≥90% mortality rate). Refractory infections with CMV, ADV and EBV are uncommon and this
represents an Orphan Disease (approximately 250 patients) in the United States. Strikingly, there is no FDA
approved therapy for this rare patient population. Recently, adoptive T-cell therapy with viral specific cytotoxic
T-lymphocytes (CTLs) is currently under early phase clinical investigations. This approach utilizes a rapid
technique of viral specific CTL isolation following specific stimulation of donor peripheral blood mononuclear
cells with viral-derived peptides followed by CTL isolation utilizing an INF-g Cytokine Capture System (Miltenyi
Prodigy). In a small number of patients in single center studies, this approach has been feasible, safe and
efficacious. The feasibility, safety and efficacy of this novel cellular therapy approach in this orphan population
in larger multicenter prospective studies is presently lacking. We therefore hypothesize that partially HLA
matched (haploidentical) related donor derived CMV, ADV and EBV CTLs manufactured utilizing the Miltenyi
CliniMACS Prodigy Cytokine Capture System will be feasible, safe and effective in CAYA with either PID
and/or SID following AlloSCT with medically refractory viral infections and/or those intolerant to antiviral
antibiotics. We will investigate this hypothesis through three large multicenter viral CTL trials (IND17449) via
the Viral CTL Consortium (VIRCTLC). The specific primary and secondary aims include (Brief): 1) feasibility
and safety of CMV, ADV and EBV CTL production and infusion; 2) efficacy of viral specific CTLs (elimination of
specific viral load by qRT-PCR below the lower limit of institutional values; 3) persistence of haploidentical
donor viral CTL infusion; secondary: 4) probability of developing AGVHD; 5) probability of viral free and overall
survival; 6) characterization of the genetic, proteomic and immunological properties of CMV, ADV and EBV
CTLs; and 7) specific T-cell immune reconstitution, function and correlation to response to viral cell therapy.
The experimental design including (brief): 1) viral CTL production by direct isolation following viral specific
peptide stimulation and cytokine capture isolation; 2) three phase II open label prospective studies; 3) viral CTL
validation and functionality; 4) viral CTL persistence by CD3 donor chimerism; and 5) viral CTL
characterization by flow cytometry, mass cytometry by time of flight (CYTOF), single cell cytokine analysis,
phosphoproteomics analysis, T-cell immunoprofiling, T cell receptor (TCR) diversity and frequency by
Immunoseq, and single cell mRNA sequencing. The long term ob...

## Key facts

- **NIH application ID:** 10244910
- **Project number:** 5R01FD006363-03
- **Recipient organization:** NEW YORK MEDICAL COLLEGE
- **Principal Investigator:** Mitchell S. Cairo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2021
- **Award amount:** $425,145
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10244910

## Citation

> US National Institutes of Health, RePORTER application 10244910, CMV, ADV and EBV Viral Cytotoxic T-Lymphocytes Generated by a Novel Cytokine Capture System in Children,Adolescents and Young Adults with Refractory Viral Infection and T-Cell Immunodeficiency (5R01FD006363-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10244910. Licensed CC0.

---

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