Exploiting cytokine secretion to rapidly produce multivirus-specific T cells for adoptive immunotherapy

Yuriko Fujita, Ann M. Leen, Jiali Sun, Yozo Nakazawa, Eric Yvon, Helen Heslop, Malcolm Brenner, Cliona M. Rooney

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Viral infections remain a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT), and conventional small-molecule therapeutics often have modest benefit, high cost, and adverse effects. Adoptive transfer of donor-derived virus-specific T cells has proved feasible and safe after HSCT and to reconstitute immunity against cytomegalovirus, Epstein-Barr virus, and adenovirus. Current protocols to generate these cytotoxic T cell lines are lengthy, taking up to 12 weeks. As viral infections often occur <30 days after HSCT, speedy production of virus-specific cytotoxic T cells lacking alloreactivity is highly desirable. We now describe a modified rapid selection method for production and characterization of CD4 + and CD8 + T cells specific for cytomegalovirus, Epstein-Barr virus, and adenovirus in a single infusate. We use Ad5f35-pp65/latent membrane protein 2 vectors in a single procedure over a 48-hour time period and manufacture a product suited for clinical use. By simultaneously expanding a portion of the selected product, we can characterize phenotype and function of the infused product and link them with subsequent in vivo outcome.

Original languageEnglish (US)
Pages (from-to)665-674
Number of pages10
JournalJournal of Immunotherapy
Volume31
Issue number7
DOIs
StatePublished - Sep 2008

Keywords

  • IFN-g selection
  • Immunotherapy
  • Stem cell transplantation
  • Viral infection

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Cancer Research
  • Pharmacology
  • Medicine(all)

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