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Tumor-targeted immune cells cure prostate cancer in mice without causing systemic immune suppression

that of TGF-beta-sensitive CD8+ T cells and 25-fold more tumor-killing activity over that of untreated CD8+ T cells.

Mice that received adoptive transfer of tumor-reactive TGF-beta-insensitive CD8+ T cells following injection of tumor cells showed no or little evidence that cancer had spread in the body.

Importantly, mice that received TGF-beta-insensitive CD8+ T cells did not develop systemic autoimmune disease, as had been the case in earlier studies by Lee and other researchers.

"To the best of our knowledge, studies to test this concept have not been attempted before," Lee said.

In summary, these CD8+ T cells were specifically reactive against tumor tissues. Second, they were insensitive to TGF-beta. The two properties endowed the CD8+T cells with the ability to infiltrate tumor tissues and function as potent effectors against tumor cells. Finally, these cells were able to persist in tumor-bearing hosts but not in those that are cancer free.

The findings of the Northwestern study provide a proof of principle that an adoptive transfer of tumor-reactive TGF-beta-insensitive CD8+ T cells may warrant consideration for the treatment of advanced tumors, Lee said.

Researchers from Northwestern University; the National Cancer Institute; Massachusetts Institute of Technology; the Fred Hutchinson Cancer Research Center; and Peking University collaborated on the study, which was supported by grants from the U.S. Department of Defense and the National Institutes of Health.


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Contact: Elizabeth Crown
e-crown@northwestern.edu
312-503-8928
Northwestern University
10-Mar-2005


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