Abstract
Human adenovirus (HAdV) infection may cause lifethreatening 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 HAdVspecific T cells in haplo-HSCT may increase the risk of graftversus- 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.
| Original language | English |
|---|---|
| Pages (from-to) | 529-536 |
| Number of pages | 8 |
| Journal | Journal of Immunotherapy |
| Volume | 31 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jul 2008 |
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Keywords
- Adenovirus infection
- Adoptive immunotherapy
- Pediatric HSCT
- T-cell lines
ASJC Scopus subject areas
- Cancer Research
- Immunology
- Immunology and Allergy
- Pharmacology
Cite this
T-cell lines specific for peptides of adenovirus hexon protein and devoid of alloreactivity against recipient cells can be obtained from HLA-haploidentical donors. / Comoli, Patrizia; Schilham, Marco W.; Basso, Sabrina; Van Vreeswijk, Tamara; Bernardo, Maria Ester; Maccario, Rita; Van Tol, M. J D; Locatelli, Franco; Veltrop-Duits, Louise A.
In: Journal of Immunotherapy, Vol. 31, No. 6, 07.2008, p. 529-536.Research output: Contribution to journal › Article
}
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 - Van Vreeswijk, Tamara
AU - Bernardo, Maria Ester
AU - Maccario, Rita
AU - Van Tol, M. J D
AU - Locatelli, Franco
AU - Veltrop-Duits, Louise A.
PY - 2008/7
Y1 - 2008/7
N2 - Human adenovirus (HAdV) infection may cause lifethreatening 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 HAdVspecific T cells in haplo-HSCT may increase the risk of graftversus- 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 lifethreatening 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 HAdVspecific T cells in haplo-HSCT may increase the risk of graftversus- 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 - Adenovirus infection
KW - Adoptive immunotherapy
KW - Pediatric HSCT
KW - T-cell lines
UR - http://www.scopus.com/inward/record.url?scp=48549101673&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=48549101673&partnerID=8YFLogxK
U2 - 10.1097/CJI.0b013e31817b9c6b
DO - 10.1097/CJI.0b013e31817b9c6b
M3 - Article
C2 - 18528302
AN - SCOPUS:48549101673
VL - 31
SP - 529
EP - 536
JO - Journal of Immunotherapy
JF - Journal of Immunotherapy
SN - 1053-8550
IS - 6
ER -