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Gene therapy protocol at UCSD activates immune system in patients with leukemia
Date:2/11/2008

A research team at the Moores Cancer Center at University of California, San Diego (UCSD) reports that patients with chronic lymphocytic leukemia (CLL) who were treated with a gene therapy protocol began making antibodies that reacted against their own leukemia cells. The study will be published on line the week of February 11-15 in the online edition of the Proceedings of the National Academy of Science.

Researchers led by Thomas J. Kipps, M.D., Ph.D., inserted a gene with the potential to activate an immune response a gene therapy protocol developed at UCSD into six patients with CLL, the most common form of adult leukemia. Several of the patients started making antibodies that reacted against their own leukemia cells. When tested in the lab, the antibodies also reacted with the leukemia cells of other patients with the disease.

The patients own leukemia cells were modified outside of their body and given back as a vaccine, said Kipps. The result raises hope that it may be possible to activate a patients immune system against their own cancer.

The patients were shown to make antibodies reactive with a leukemia-associated antigen a protein made by leukemia cells that can stimulate the body's immune system to produce antibodies called ROR1. This antigen appears to be found only on the cell surface of the leukemia cells, but not on normal cells, and serves as a receptor that binds to a ligand called Wnt5a, which activates a pathway important for the survival of the leukemia cells.

The Wnt5a ligand interacts with ROR1 to enhance leukemia-cell survival. Antibodies that react with ROR1 can interfere with this survival signal and might also specifically target the leukemia cells for destruction, Kipps said.

He also noted that because the ROR1 antigen is found only on leukemia cells, it could be developed as a very specific marker to monitor for the continued presence of leukemia cells after treatment or for i
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Contact: Debra Kain
ddkain@ucsd.edu
619-543-6163
University of California - San Diego
Source:Eurekalert

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