Third Party Viral Specific T-cells (VSTs)

Third Party Viral Specific T-cells (VSTs) for Treatment of Viral Infections in Immunocompromised Patients

The purpose of this study is to demonstrate that viral specific T-cells (a type of white blood cell) can be generated from an unrelated donor and given safely to patients with viral infections.

Study Overview

• Status: Recruiting
• Conditions: Viral Infection; Viral Reactivation; Infection in an Immunocompromised Host
• Intervention / Treatment: Biological: Viral Specific VST Infusion

Detailed Description

Viral reactivation and infection is a major cause of morbidity in immunocompromised patients (including HSCT recipients). In this study we will draw blood from unrelated (third party) donors and use the blood to generate viral specific T-cells (VSTs) with specificity for Epstein-Barr virus (EBV), cytomegalovirus (CMV), adenovirus (ADV), BK virus (BKV), and JC Virus. The VSTs will be infused into immunocompromised children with specific viral infections (EBV, CMV, ADV, BKV , or JC virus). Cells will be selected for infusion based on the recipient's HLA type and the viral specificity of the cells.

• Study Type: Interventional
• Enrollment (Estimated): 750
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jamie Wilhelm; Phone Number: (513) 803-1102; Email: Jamie.Wilhelm@cchmc.org
• Study Contact Backup: Name: Michael Grimley, MD; Email: Michael.Grimley@cchmc.org

Study Locations

• United States
  • Ohio
    • Akron, Ohio, United States, 44308
      • Recruiting
      • Akron Children's Hospital
      • Contact: Courtney Culbertson, CNP; Phone Number: 330-543-3338; Email: cculbertson@akronchildrens.org
      • Principal Investigator: Megan Sampson, MD
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital Medical Center
      • Contact: Jamie Wilhelm; Phone Number: 513-803-1102; Email: Jamie.Wilhelm@cchmc.org
      • Principal Investigator: Michael Grimley, MD
    • Cincinnati, Ohio, United States, 45219
      • Completed
      • University of Cincinnati Medical Center
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University Wexner Medical Center - James Cancer Hospital
      • Principal Investigator: Polina Shindiapina, MD, PhD
      • Contact: Nicole Szuminski, MS, RN, CCRC; Email: nicole.szuminski@osumc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 days and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Immunocompromised patient with evidence of viral infection or reactivation
• Age >1 day
• Recipients who have had a stem cell transplant must be at least 21 days after stem cell infusion
• Clinical status must allow tapering of steroids to < 0.5mg/kg prednisone or other steroid equivalent
• Must be able to receive CTL infusion in Cincinnati
• Informed consent obtained by PI or sub-investigator either in person or by phone

Exclusion Criteria:

• Active acute GVHD grades II-IV
• Uncontrolled bacterial or fungal infection
• Uncontrolled relapse of malignancy requiring treatment with chemotherapy
• Infusion of ATG or alemtuzumab within 2 weeks of VST infusion
• Biopsy confirmed acute rejection of solid organ transplant OR empiric treatment of suspected but not confirmed acute rejection of solid organ transplant within the last 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Viral Specific VST Infusion; 3rd party VST infusion

Biological: Viral Specific VST Infusion; VSTs will be infused into immunocompromised patients with evidence of viral infection or reactivation defined as any of the following: Blood adenovirus PCR ≥ 1,000; Blood CMV PCR ≥ 500; Blood EBV PCR ≥ 9,000; Plasma BKV PCR >1,000; Plasma JC Virus PCR > 1,000; Evidence of invasive adenovirus infection or disease, defined as the presence of adenoviral positivity by PCR or culture in one or more sites; Evidence of invasive CMV infection, eg pneumonitis, retinitis, colitis; Evidence of invasive EBV disease/infection, EBV-associated lymphoproliferation (EBV-LPD) defined as proven EBV-LPD by biopsy or probable EBV-LPD defined as an elevated EBV DNA level in the blood associated with clinical symptoms (adenopathy or fever or masses on imaging) but without biopsy confirmation, or EBV-associated malignancies; Evidence of symptomatic BK virus infection, which may include symptomatic hemorrhagic cystitis, or BK nephropathy; Evidence of PML or other CNS infection due to JC virus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful production of viral specific T-cells	Of the patients who had a VST culture initiated, successful production of VST cells is defined as meeting the protocol-defined release criteria.	Within 30 days post culture initiation
Percentage of patients who do not have infusional toxicity	Patients will be monitored for infusional toxicity	Through 30 minutes post infusion
Incidence of GVHD associated with VST infusion	Patients will be monitored for the development of VST associated GVHD	Through 30 days after infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of viral-specific T-cells	Presence of viral-specific T-cells in the participant's blood will be assessed by Elispot assay	At 30 days after infusion
Viral burden	The viral burden will be assessed using the protocol-defined efficacy assessment.	At 30 days after infusion

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Investigators: Principal Investigator: Michael Grimley, MD, MD, Children's Hospital Medical Center, Cincinnati

Publications and helpful links

General Publications

• Rubinstein JD, Zhu X, Leemhuis T, Pham G, Ray L, Emberesh S, Jodele S, Thomas S, Cancelas JA, Bollard CM, Hanley PJ, Keller MD, Grimley O, Clark D, Clark T, Lindestam Arlehamn CS, Sette A, Davies SM, Nelson AS, Grimley MS, Lutzko C. Virus-specific T cells for adenovirus infection after stem cell transplantation are highly effective and class II HLA restricted. Blood Adv. 2021 Sep 14;5(17):3309-3321. doi: 10.1182/bloodadvances.2021004456.
• Nelson AS, Heyenbruch D, Rubinstein JD, Sabulski A, Jodele S, Thomas S, Lutzko C, Zhu X, Leemhuis T, Cancelas JA, Keller M, Bollard CM, Hanley PJ, Davies SM, Grimley MS. Virus-specific T-cell therapy to treat BK polyomavirus infection in bone marrow and solid organ transplant recipients. Blood Adv. 2020 Nov 24;4(22):5745-5754. doi: 10.1182/bloodadvances.2020003073.
• Rubinstein JD, Pham G, Sridharan A, Khoury R, Wang YM, Hudda Z, Wilhelm J, Lichtenstein D, Heyenbruch D, Cancelas JA, Davies SM, Lutzko C, Grimley M. Outcomes with Third Party Virus Specific T-cells After the Use of Single Antigen Cell Lines to Predict HLA Restriction. Blood Adv. 2025 Sep 24:bloodadvances.2025017097. doi: 10.1182/bloodadvances.2025017097. Online ahead of print.
• Galletta TJ, Lane A, Lutzko C, Leemhuis T, Cancelas JA, Khoury R, Wang YM, Hanley PJ, Keller MD, Bollard CM, Davies SM, Grimley MS, Rubinstein JD. Third-Party and Patient-Specific Donor-Derived Virus-Specific T Cells Demonstrate Similar Efficacy and Safety for Management of Viral Infections after Hematopoietic Stem Cell Transplantation in Children and Young Adults. Transplant Cell Ther. 2023 May;29(5):305-310. doi: 10.1016/j.jtct.2023.01.027. Epub 2023 Feb 3.

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2015
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: August 21, 2015
• First Submitted That Met QC Criteria: August 21, 2015
• First Posted (Estimated): August 25, 2015

Study Record Updates

• Last Update Posted (Estimated): December 16, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: T-Cells; Cytomegalovirus (CMV); Epstein-Barr Virus (EBV); Adenovirus (ADV); Donor; BK virus (BKV)
• Additional Relevant MeSH Terms: Infections; DNA Virus Infections; Herpesviridae Infections; Tumor Virus Infections; Virus Diseases; Epstein-Barr Virus Infections; Adenoviridae Infections
• Other Study ID Numbers: 2015-4184

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No