Last month, Penn Medicine put out a press release heralding a “cancer treatment breakthrough 20 years in the making.” In a small clinical trial, three patients with advanced chronic lymphocytic leukemia (CLL) were treated with genetically engineered versions of their own T cells. Just a few weeks after treatment the tumors had disappeared, and the patients remained in remission for a year before the study was published.
The release didn’t, however, explain those “20 years in the making.” In 1989, Prof. Zelig Eshhar of the Weizmann Institute’s Immunology Department first published a paper describing a method of creating gene-modified T cells by adding on chimeric molecules that functioned as receptors with the specificity of an antibody. The idea, from the beginning, was that these immune cells could be programmed to identify and coordinate an attack against such cells as cancer cells, which generally manage to evade the immune system. The engineering method used by the Penn team is the one Eshhar began developing in the 1980s. For Eshhar, the new study is proof of concept; it had previously been shown to work in mice. Now that the method has been successfully used in humans – and the results even better than anyone dared hope – it can be tried on a wider scale for other types of cancer.
If the idea seems futuristic now, it was downright science fiction, then. More importantly, those first chimeric T cells were created in a lab dish and sent off to attack other cells in a lab dish. Those twenty years reflect the time it takes to move from a revolutionary idea that works in the lab to a medical treatment that works on humans. In light of the many potential anti-cancer treatments that fail somewhere along the way from lab to clinic, the new study is a triumph both for the Penn team and for Eshhar and his team.
This is clearly the place to repeat our mantra about basic research: It is a long-term undertaking. There are no guarantees. No one can predict where a specific line of inquiry will eventually lead, or when. Without basic research and vision, there will be no innovative new cancer treatments.
Eshhar, by the way, recently improved on the genetically engineered T cell idea by creating them from a non-matched donor pool, rather than cells extracted from the individual patient. In mouse experiments, he and his team temporarily suppressed the immune system with a mild dose of radiation and then administered the donor chimeric T cells. Because the method destroys tumors so quickly and effectively, these cells had time to finish the job before the immune system came back online and rejected them.
How long will it take for this improved method to reach the clinic? For our answer, see paragraph four. Or keep posted here.