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Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes

Lookup NU author(s): Professor Andrew GenneryORCiD, Professor Mary Slatter


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Background: Viral infections are a leading fatal complication for patients with primary immunodeficiencies (PIDs) who require hematopoietic stem cell transplantation (HSCT). Use of virus-specific T lymphocytes (VSTs) has been successful for the treatment and prevention of viral infections after HSCT for malignant and nonmalignant conditions. Here we describe the clinical use of VSTs in patients with PIDs at 4 centers.Objective: We sought to evaluate the safety and efficacy of VSTs for treatment of viral infections in patients with PIDs.Methods: Patients with PIDs who have received VST therapy on previous or current protocols were reviewed in aggregate. Clinical information, including transplantation details, viral infections, and use of antiviral and immunosuppressive pharmacotherapy, were evaluated. Data regarding VST production, infusions, and adverse reactions were compared.Results: Thirty-six patients with 12 classes of PID diagnoses received 37 VST products before or after HSCT. Twenty-six (72%) patients had received a diagnosis of infection with cytomegalovirus, EBV, adenovirus, BK virus, and/or human herpesvirus 6. Two patients were treated before HSCT because of EBV-associated lymphoproliferative disease. Partial or complete responses against targeted viruses occurred in 81% of patients overall. Time to response varied from 2 weeks to 3 months ( median, 28 days). Overall survival at 6 months after therapy was 80%. Four patients had graft-versus-host disease in the 45 days after VST infusion, which in most cases was therapy responsive.Conclusion: VSTs derived from either stem cell donors or third-party donors are likely safe and effective for the treatment of viral infections in patients with PIDs.

Publication metadata

Author(s): Naik S, Nicholas SK, Martinez CA, Leen AM, Hanley PJ, Gottschalk SM, Rooney CM, Hanson IC, Krance RA, Shpall EJ, Cruz CR, Amrolia P, Lucchini G, Bunin N, Heimall J, Klein OR, Gennery AR, Slatter MA, Vickers MA, Orange JS, Heslop HE, Bollard CM, Keller MD

Publication type: Article

Publication status: Published

Journal: Journal of Allergy and Clinical Immunology

Year: 2016

Volume: 137

Issue: 5

Pages: 1498-1505.e1

Print publication date: 01/05/2016

Online publication date: 24/02/2016

Acceptance date: 14/12/2015

ISSN (print): 0091-6749

ISSN (electronic): 1097-6825

Publisher: Mosby, Inc.


DOI: 10.1016/j.jaci.2015.12.1311


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Funder referenceFunder name
American Academy of Allergy, Asthma Immunology
American College of Allergy, Asthma Immunology
Amy Strelzer Manasevit Scholar Award
Clinical and Translational Science Institute at Children's National
Jeffrey Modell Diagnostic and Research Center Grant
Jeffrey Modell Foundation
Clinical Immunology Society
Clinical Research Center at Texas Children's Hospital
Dan L. Duncan Institute for Clinical and Translational Research at Baylor College of Medicine
SCOR from the Leukemia and Lymphoma Society
HHSN268201000007CProduction Assistance for Cellular Therapies (PACT) program (NHLBI)
P50CA126752National Institutes of Health
PO1 CA148600e02National Cancer Institute
U54 HL081007National Institutes of Health
RO1CA061384National Institutes of Health