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New approach supercharges immunotherapy

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"This discovery addresses the basic question facing cancer immunotherapy," said Liebowitz: "Why are the T cells that should attack tumors content to sit idly by? Previous efforts to jump start an immune response have not been able effectively to reverse the immune tolerance that develops between a patient's T cells and their cancer."

But by growing billions of a patient's T cells in the laboratory, away from tumor cells and under constant co-stimulation with CD3 and CD28, Liebowitz's team has been able to reactivate the immune response, returning a population of aggressive, "motivated" cells to seek out and attack cancerous cells.

"Co-stimulation gives us a completely different population of T cells," said Liebowitz. Prior attempts have produced large numbers of cytotoxic T cells, which are the end product of an immune response. Growth in the presence of CD3 and CD28, however, produces primarily T-helper cells, so called because they coordinate the actions of the entire immune system."

This is the only system currently in use that favors the growth of T-helper cells over cytotoxic cells.

A few weeks after receiving their new, improved T-helper cells, some patients have experienced fevers and lethargy while their T-cell counts continue to rise. Over the following weeks and months, much too slowly to be a late response to prior chemotherapy, their tumors get smaller and in some cases have disappeared.

"We know we are affecting the immune response with this therapy because the toxicities we have seen after reinfusion look exactly like autoimmune disorders," (in which an over-aggressive immune system attacks its host) said Liebowitz.

Although the side effects of reinfusing the rejuvenated T cells appear to be limited, the entire treatment protocol is quite rigorous. Treatment involves collecting and storing stem cells from the patient's blood, administering high-dose c
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Contact: John Easton
jeaston@mcis.bsd.uchicago.edu
773-702-6241
University of Chicago Medical Center
5-Dec-1998


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