Generation of polyclonal CMV-specific T cells for the adoptive immunotherapy of glioblastoma

Alexia Ghazi, Aidin Ashoori, Patrick J. Hanley, Vita S. Brawley, Donald R. Shaffer, Yvonne Kew, Suzanne Z. Powell, Robert Grossman, Zakaria Grada, Michael E. Scheurer, Meenakshi Hegde, Ann M. Leen, Catherine M. Bollard, Cliona M. Rooney, Helen E. Heslop, Stephen Gottschalk, Nabil Ahmed

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Glioblastoma (GBM) is the most common primary brain cancer in adults and is virtually incurable. Recent studies have shown that cytomegalovirus (CMV) is present in majority of GBMs. To evaluate whether the CMV antigens pp65 and IE1, which are expressed in GBMs, could be targeted by CMV-specific T cells, we measured the frequency of T cells targeting pp65 and IE1 in the peripheral blood of a cohort of 11 sequentially diagnosed CMV-seropositive GBM patients, and evaluated whether it was feasible to expand autologous CMV-specific T cells for future clinical studies. All 11 CMV-seropositive GBM patients had T cells specific for pp65 and IE1 in their peripheral blood assessed by IFNγ enzyme-linked immunospot assay. However, the precursor frequency of pp65-specific T cells was decreased in comparison with healthy donors (P=0.001). We successfully reactivated and expanded CMV-specific T cells from 6 out of 6 GBM patients using antigen-presenting cells transduced with an adenoviral vector encoding pp65 and IE1. CMV-specific T-cell lines contained CD4 + as well as CD8 + T cells, recognized pp65 + and IE1 + targets and killed CMV-infected autologous GBM cells. Infusion of such CMV-specific T-cell lines may extend the benefits of T-cell therapy to patients with CMV + GBMs.

Original languageEnglish (US)
Pages (from-to)159-168
Number of pages10
JournalJournal of Immunotherapy
Volume35
Issue number2
DOIs
StatePublished - Feb 2012

Keywords

  • CMV
  • GBM
  • glioblastoma
  • IE1
  • immunotherapy
  • pp65
  • T cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Cancer Research
  • Pharmacology

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