Nucleofection of DCs to generate multivirus-specific T cells for prevention or treatment of viral infections in the immunocompromised host

Ulrike Gerdemann, Anne S. Christin, Juan F. Vera, Carlos A. Ramos, Yuriko Fujita, Hao Liu, Dagmar Dilloo, Helen E. Heslop, Malcolm K. Brenner, Cliona M. Rooney, Ann M. Leen

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Viral infections cause morbidity and mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. To prevent and treat these, we have produced and infused cytotoxic T lymphocytes (CTLs) with specificity for Epstein-Barr virus (EBV), cytomegalovirus (CMV), and adenovirus (Adv), and shown that small numbers of infused cells proliferate in vivo and protect against all three viruses. Despite these encouraging results, broader implementation of this approach is limited by the need for infectious virus material (EBV), expensive production of clinical grade adenoviral vectors, and a prolonged (8-12 weeks) period of manufacture. There is also competition between virus-derived antigens within antigen-presenting cells (APCs), limiting extension to additional agents. We now describe an approach that uses DNA nucleofection of dendritic cells (DCs) with DNA plasmids that encode a range of immunodominant and subdominant viral antigens from CMV, EBV, BK, and Adv. Within 10 days, this methodology provides multivirus-reactive CTLs that lack alloreactivity. We further demonstrate that nucleofected DC stimulation can be combined with interferon-γ (IFN-γ) capture technology to produce even more rapid multivirus-CTL products for treatment of acute infection. These CTL generation procedures should increase the feasibility and applicability of T-cell therapy.

Original languageEnglish (US)
Pages (from-to)1616-1625
Number of pages10
JournalMolecular Therapy
Volume17
Issue number9
DOIs
StatePublished - Jul 8 2009
Externally publishedYes

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Immunocompromised Host
Cytotoxic T-Lymphocytes
Virus Diseases
Dendritic Cells
Human Herpesvirus 4
T-Lymphocytes
Viruses
Cytomegalovirus
Adenoviridae
Viral Antigens
DNA
Antigen-Presenting Cells
Therapeutics
Cell- and Tissue-Based Therapy
Hematopoietic Stem Cells
Interferons
Plasmids
Cell Count
Technology
Morbidity

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Nucleofection of DCs to generate multivirus-specific T cells for prevention or treatment of viral infections in the immunocompromised host. / Gerdemann, Ulrike; Christin, Anne S.; Vera, Juan F.; Ramos, Carlos A.; Fujita, Yuriko; Liu, Hao; Dilloo, Dagmar; Heslop, Helen E.; Brenner, Malcolm K.; Rooney, Cliona M.; Leen, Ann M.

In: Molecular Therapy, Vol. 17, No. 9, 08.07.2009, p. 1616-1625.

Research output: Contribution to journalArticle

Gerdemann, U, Christin, AS, Vera, JF, Ramos, CA, Fujita, Y, Liu, H, Dilloo, D, Heslop, HE, Brenner, MK, Rooney, CM & Leen, AM 2009, 'Nucleofection of DCs to generate multivirus-specific T cells for prevention or treatment of viral infections in the immunocompromised host', Molecular Therapy, vol. 17, no. 9, pp. 1616-1625. https://doi.org/10.1038/mt.2009.140
Gerdemann, Ulrike ; Christin, Anne S. ; Vera, Juan F. ; Ramos, Carlos A. ; Fujita, Yuriko ; Liu, Hao ; Dilloo, Dagmar ; Heslop, Helen E. ; Brenner, Malcolm K. ; Rooney, Cliona M. ; Leen, Ann M. / Nucleofection of DCs to generate multivirus-specific T cells for prevention or treatment of viral infections in the immunocompromised host. In: Molecular Therapy. 2009 ; Vol. 17, No. 9. pp. 1616-1625.
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