TY - JOUR
T1 - T-cell Lines Specific for Peptides of Adenovirus Hexon Protein and Devoid of Alloreactivity Against Recipient Cells can be Obtained From HLA-haploidentical Donors
AU - Comoli, Patrizia
AU - Schilham, Marco W.
AU - Basso, Sabrina
AU - Vreeswijk, Tamara van
AU - Bernardo, Maria Ester
AU - Maccario, Rita
AU - Tol, Maarten J. D. van
AU - Locatelli, Franco
AU - Veltrop-Duits, Louise A.
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
KW - pediatric HSCT
KW - adoptive immunotherapy
KW - T-cell lines
KW - adenovirus infection
KW - pediatric HSCT
KW - adoptive immunotherapy
KW - T-cell lines
KW - adenovirus infection
UR - http://hdl.handle.net/10807/258376
U2 - 10.1097/cji.0b013e31817b9c6b
DO - 10.1097/cji.0b013e31817b9c6b
M3 - Article
SN - 1524-9557
VL - 31
SP - 529
EP - 536
JO - Journal of Immunotherapy
JF - Journal of Immunotherapy
ER -