Researchers have used genetic engineering to create a new type of cell line that removes a significant barrier to the practical use of immunotherapy - the difficulty of producing sufficient numbers of immune cells capable of killing diseased tissues. Arming and training a patient’s own white blood cells to more vigorously attack tumors or virus-infected cells shows promise for fighting disease. If only these white cells - or cytotoxic T cells (CTLs) - could be produced in high enough numbers, the body could be trained to seek out and destroy diseased tissues by itself. One way of doing this is to remove CTLs from a patient’s blood, thereby removing the blood factors and immune-regulatory mechanisms that normally prevent them from attacking target cells. Once outside the body, CTLs can be transformed into killers, and then reintroduced into the patient’s blood, where they circulate and fight disease.
Unfortunately, inducing the proliferation of CTLs in sufficient numbers outside the body has proven very tricky. This is because researchers are still learning how a second type of cells - antigen-presenting cells (APCs) - “present” tumor antigens to CTLs and trigger their activation and multiplication. Ideally, APCs are also taken from a patient, but this has proved problematic because they are difficult to obtain and very variable in their activity. Now, Carl June and colleagues think that they might have come up with an alternative (Nature Biotechnology, Vol. 20, No. 2, 01 Feb 02). They have engineered a cell line to express a set of stimulatory signals that mimics APCs and appears effective in producing large numbers of CTLs capable of killing diseased cells.
As a starting strategy, the researchers engineered a human cell line to express two types of antibody receptor (the human Fcã receptor and CD32), which were then combined with antibodies previously shown to promote the growth of another type of white blood cell (helper T cells). They also engineered another molecule (4-1BB ligand) found on natural APCs to see if it could promote the long-term growth of CTLs outside of the body. What they then found was that the resulting cell line could be used to stimulate long-term expansion of CTLs, while maintaining their ability to kill cells infected with virus. Moreover, CTLs proliferated in sufficient numbers to make transfer back to patients feasible.
The authors believe the cell line represents a more reliable and defined alternative to APCs obtained from the patient. It promises to make more practical clinical applications of CTLs against tumors and viruses.
Carl H. June
Department of Pathology and Laboratory Medicine
University of Pennsylvania
Philadelphia, PA 19104
(News and Views)
Mark E. Dudley
National Cancer Institute
Bethesda, MD 20892
(C) Nature Biotechnology press release.
Message posted by: Trevor M. D'Souza
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