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Blood, 15 March 2002, Vol. 99, No. 6, pp. 2009-2016
GENE THERAPY
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, and
Malcolm K. Brenner
From the Center for Cell and Gene Therapy and the
DeBakey Department of Surgery, Baylor College of Medicine, Houston,
Texas.
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 cytotoxic 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.
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