T-cell lines specific for peptides of adenovirus hexon protein and devoid of alloreactivity against recipient cells can be obtained from HLA-haploidentical donors.
Human adenovirus (HAdV) infection may cause life-threatening complications in recipients of hematopoietic stem cell transplantation (HSCT), the highest risk being observed in children given T-cell depleted haploidentical allografts. The effectiveness of pharmacologic therapy for HAdV infection is suboptimal. Recently, cell therapy was demonstrated to offer a unique opportunity to restore antiviral immune surveillance, leading to clearance of infection and prevention/treatment of disease. However, infusion of insufficiently selected HAdV-specific T cells in haplo-HSCT may increase the risk of graft-versus-host disease. We conducted scale-up experiments to validate a method of in vitro culture to expand T cells specific for HAdV from donor peripheral blood mononuclear cells (PBMC), based on stimulation with a pool of five 30-mer peptides derived from HAdV5 hexon protein, for use in recipients of haplo-HSCT. A total of 21 T-cell lines that included a majority of CD4 T lymphocytes, were generated. Nineteen of the 21 T-cell lines proliferated specifically against HAdV. The 2 nonspecific, and 3 T-cell lines with lower specific activity, included a median of 48% CD8 T cells. The 19 HAdV-specific T-cell lines showed a median 357-fold decrease in alloreactivity, compared with proliferation of noncultured donor PBMC in response to recipient PBMC, only 4/19 T-cell lines showing residual alloreactivity. Our data indicate that HAdV-specific CD4 T-cell lines with efficient in vitro antiviral response and low/undetectable alloreactivity against recipient targets may be expanded from PBMC of most human leukocyte antigen-haploidentical HSCT donors after stimulation with HAdV hexon protein-derived peptides. These T cells may be safely employed for adoptive treatment of HAdV complications.
Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy. pcomoli@smatteo.pv.it
Patrizia
P
Comoli
Marco W
MW
Schilham
Sabrina
S
Basso
Tamara
T
van Vreeswijk
Maria Ester
ME
Bernardo
Rita
R
Maccario
Maarten J D
MJ
van Tol
Franco
F
Locatelli
Louise A
LA
Veltrop-Duits
D036022:Capsid Proteins / Q000276:immunology*; D002460:Cell Line; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology*; D014019:Tissue Donors
D036022:Capsid Proteins; C018315:hexon capsid protein, Adenovirus; D007371:Interferon-gamma