Epstein-Barr virus-specific human T lymphocytes expressing antitumor chimeric T-cell receptors: Potential for improved immunotherapy

Claudia Rossig, Catherine M. Bollard, Jed G. Nuchtern, Cliona M. Rooney, Malcolm Brenner

Research output: Contribution to journalArticle

167 Scopus citations

Abstract

Primary T cells expressing chimeric receptors specific for tumor or viral antigens have considerable therapeutic potential. Unfortunately, their clinical value is limited by their rapid loss of function and failure to expand in vivo, presumably due to the lack of costimulator molecules on tumor cells and the inherent limitations of signaling exclusively through the chimeric receptor. Epstein-Barr virus (EBV) infection of B lymphocytes is near universal in humans and stimulates high levels of EBV-specific helper and cyto-toxic T cells, which persist indefinitely. Our clinical studies have shown that EBV-specific T cells generated in vitro will expand, persist, and function for more than 6 years in vivo. We now report that EBV-specific (but not primary) T cells transduced with tumor-specific chimeric receptor genes can be expanded and maintained long-term in the presence of EBV-infected B cells. They recognize EBV-infected targets through their conventional T-cell receptor and tumor targets through their chimeric receptors. They efficiently lyse both. EBV-specific T cells expressing chimeric antitumor receptors may represent a new source of effector cells that would persist and function long-term after their transfer to cancer patients.

Original languageEnglish (US)
Pages (from-to)2009-2016
Number of pages8
JournalBlood
Volume99
Issue number6
DOIs
StatePublished - Mar 15 2002

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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