T-cell lines specific for peptides of adenovirus hexon protein and devoid of alloreactivity against recipient cells can be obtained from HLA-haploidentical donors

Patrizia Comoli, Marco W. Schilham, Sabrina Basso, Tamara Van Vreeswijk, Maria Ester Bernardo, Rita Maccario, M. J D Van Tol, Franco Locatelli, Louise A. Veltrop-Duits

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 languageEnglish
Pages (from-to)529-536
Number of pages8
JournalJournal of Immunotherapy
Volume31
Issue number6
DOIs
Publication statusPublished - Jul 2008

Fingerprint

Tissue Donors
T-Lymphocytes
Human Adenoviruses
Cell Line
Peptides
Hematopoietic Stem Cell Transplantation
Human Adenovirus Infections
Blood Cells
Antiviral Agents
Adenovirus hexon capsid protein
HLA Antigens
Cell- and Tissue-Based Therapy
Allografts
Therapeutics
Infection

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 journalArticle

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. / T-cell lines specific for peptides of adenovirus hexon protein and devoid of alloreactivity against recipient cells can be obtained from HLA-haploidentical donors. In: Journal of Immunotherapy. 2008 ; Vol. 31, No. 6. pp. 529-536.
@article{ee9a608bd21043b69cc4207b97ec5358,
title = "T-cell lines specific for peptides of adenovirus hexon protein and devoid of alloreactivity against recipient cells can be obtained from HLA-haploidentical donors",
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.",
keywords = "Adenovirus infection, Adoptive immunotherapy, Pediatric HSCT, T-cell lines",
author = "Patrizia Comoli and Schilham, {Marco W.} and Sabrina Basso and {Van Vreeswijk}, Tamara and Bernardo, {Maria Ester} and Rita Maccario and {Van Tol}, {M. J D} and Franco Locatelli and Veltrop-Duits, {Louise A.}",
year = "2008",
month = "7",
doi = "10.1097/CJI.0b013e31817b9c6b",
language = "English",
volume = "31",
pages = "529--536",
journal = "Journal of Immunotherapy",
issn = "1053-8550",
publisher = "Lippincott Williams and Wilkins",
number = "6",

}

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 -