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Blood, 1 February 2004, Vol. 103, No. 3, pp. 1011-1019.
Prepublished online as a Blood First Edition Paper on October 2, 2003; DOI 10.1182/blood-2003-07-2449.


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Submitted July 21, 2003
Accepted September 28, 2003

Fiber-modified adenoviruses generate sub-group cross-reactive, adenovirus-specific cytotoxic T lymphocytes for therapeutic applications

Ann M Leen, Uluhan Sili, Barbara Savoldo, Alan M Jewell, Pedro A Piedra, Malcolm K Brenner, and Cliona M Rooney*

Department of Pediatrics and Medicine, Center for Cell and Gene Therapy, Houston, Texas, USA
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
Department of Pediatrics and Medicine, Center for Cell and Gene Therapy, Houston, Texas, USA; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA

* Corresponding author; email: cmrooney{at}texaschildrenshospital.org.

Adenovirus (Ad) infections are responsible for considerable morbidity and mortality, particularly in pediatric hematopoietic stem cell transplant (HSCT) recipients. To date there is no therapy. The present study was motivated by the potential for using adoptive immunotherapy as either prophylaxis or treatment for Ad infections and associated diseases. The authors have developed a protocol to reactivate Ad-specific memory T cells from peripheral blood mononuclear cells (PBMCs), using a clinical grade adenoviral vector. Such lines contain a specific CD4 and CD8 T cell component, and are capable of recognizing and lysing target cells infected with wild-type Ad serotypes from different Ad groups. Furthermore, the frequency of Ad-specific precursors can be determined in PBMCs ex vivo, and used as a means to assess changes in Ad-specific T cell memory responses post-infusion. This is the first report of a simple and reproducible method to activate and expand Ad-specific cytotoxic T lymphocytes (CTL), which should be protective against the range of different Ad subtypes that affect transplant recipients.


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