Fiber-modified adenoviruses generate subgroup cross-reactive, adenovirus-specific cytotoxic T lymphocytes for therapeutic applications.
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 after infusion. This is the first report of a simple and reproducible method to activate and expand Ad-specific cytotoxic T lymphocytes (CTLs), which should be protective against the range of different Ad subtypes that affect transplant recipients.
Leen
Ann M
AM
Center for Cell and Gene Therapy, Department of Pediatrics, 6621 Fannin S, MC 3-3320, Houston, TX 77030, USA.
Sili
Uluhan
U
Savoldo
Barbara
B
Jewell
Alan M
AM
Piedra
Pedro A
PA
Brenner
Malcolm K
MK
Rooney
Cliona M
CM
D000256:Adenoviridae / Q000145:classification / Q000235:genetics / Q000276:immunology*; D000257:Adenoviridae Infections / Q000209:etiology / Q000517:prevention & control / Q000628:therapy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003429:Cross Reactions; D003713:Dendritic Cells / Q000276:immunology; D005822:Genetic Vectors; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive / Q000379:methods*; D066298:In Vitro Techniques; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation