Safety and clinical efficacy of rapidly-generated trivirus-directed T cells as treatment for adenovirus, EBV, and CMV infections after allogeneic hematopoietic stem cell transplant

Ulrike Gerdemann, Usha L. Katari, Anastasia Papadopoulou, Jacqueline M. Keirnan, John A. Craddock, Hao Liu, Caridad A. Martinez, Alana Kennedy-Nasser, Kathryn S. Leung, Stephen M. Gottschalk, Robert A. Krance, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Ann M. Leen

Research output: Contribution to journalArticle

135 Scopus citations

Abstract

Adoptive transfer of virus-specific T cells can prevent and treat serious infections with Epstein-Barr virus (EBV), cytomegalovirus (CMV), and adenovirus (Adv) after allogeneic hematopoietic stem cell transplant. It has, however, proved difficult to make this approach widely available since infectious virus and viral vectors are required for T cell activation, followed by an intensive and prolonged culture period extending over several months. We now show that T cells targeting a range of viral antigens derived from EBV, CMV, and Adv can be reproducibly generated in a single culture over a 2-3-week period, using methods that exclude all viral components and employ a much-simplified culture technology. When administered to recipients of haploidentical (n = 5), matched unrelated (n = 3), mismatched unrelated (n = 1) or matched related (n = 1) transplants with active CMV (n = 3), Adv (n = 1), EBV (n = 2), EBV+Adv (n = 2) or CMV+Adv (n = 2) infections, the cells produced complete virological responses in 80%, including all patients with dual infections. In each case, a decrease in viral load correlated with an increase in the frequency of T cells directed against the infecting virus(es); both immediate and delayed toxicities were absent. This approach should increase both the feasibility and applicability of T cell therapy. The trial was registered at www.clinicaltrials.gov as NCT01070797.

Original languageEnglish (US)
Pages (from-to)2113-2121
Number of pages9
JournalMolecular Therapy
Volume21
Issue number11
DOIs
StatePublished - Nov 2013
Externally publishedYes

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Safety and clinical efficacy of rapidly-generated trivirus-directed T cells as treatment for adenovirus, EBV, and CMV infections after allogeneic hematopoietic stem cell transplant'. Together they form a unique fingerprint.

  • Cite this

    Gerdemann, U., Katari, U. L., Papadopoulou, A., Keirnan, J. M., Craddock, J. A., Liu, H., Martinez, C. A., Kennedy-Nasser, A., Leung, K. S., Gottschalk, S. M., Krance, R. A., Brenner, M. K., Rooney, C. M., Heslop, H. E., & Leen, A. M. (2013). Safety and clinical efficacy of rapidly-generated trivirus-directed T cells as treatment for adenovirus, EBV, and CMV infections after allogeneic hematopoietic stem cell transplant. Molecular Therapy, 21(11), 2113-2121. https://doi.org/10.1038/mt.2013.151