Scientists have coopted immune cells as agents for delivering anticancer gene therapy. Although the system is far from testing in humans, the approach could complement more traditional cancer treatments such as chemotherapy.
Although cancer gene therapy is a potentially powerful adjunct to conventional cancer therapies, its use in clinical settings has been severely limited due to the undesirable foreign gene expression in tissues other than the tumor. To create a gene therapy delivery system more specific to tumors, researchers led by Richard Vile have employed T cells, a class of immune cells that preferentially targets tumors as a means of delivering a “suicide” gene to cancer cells (Nature Biotechnology, Vol. 20, No. 3, March 1, 2002).
The researchers first set about tailoring T cells to be specific to tumors by incorporating into their DNA a gene expressing a receptor that binds to a tumor-specific cell-surface protein called carcinoembryonic antigen (CEA). To turn the T cells into potent cancer-killing agents, they were engineered to produce a virus carrying a toxic gene (thymidine kinase). This gene, which originates from herpes simplex virus and is not normally present in cells, encodes a protein that converts a relatively harmless prodrug, ganciclovir, into a cancer killing poison. To add an even greater level of control, they also placed the thymidine kinase gene under the control of a regulatory element (the CEA promoter) that is active only in tumor cells.
The authors demonstrate the potency of their approach both in tissue culture as well as in mice with lung and liver metastases. Further studies—for example, to make sure that enough virus is produced by the T cells during their lifetime in the body—will be required before this system can be tested in humans.
Molecular Medicine Program
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E. Antonio Chiocca
Molecular Neuro-oncology and Neurosurgery
Massachusetts General Hospital
Harvard Medical School
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