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“We’re feeling the ground shaking under our feet”: Stanford oncologist talks cancer immunotherapy

Levy 2004Stanford’s reputation as a powerhouse of award-winning research is well-earned — but only occasionally do so many of its stellar scientists gather at the same time to hear one of their own speak. When, however, long-time Stanford oncologist Ronald Levy, MD, delivered a recent lecture with the title of “Immunotherapy comes of age,” a large number of well-known names in medicine were among those in the standing-room-only crowd.

Levy himself called out one particular member of that audience — his mentor Saul Rosenberg, MD, who was recruited to Stanford by radiologist Henry Kaplan, MD. Just as Kaplan and Rosenberg teamed to transform Hodgkin’s disease from unbeatable to one of the most curable cancers, Levy is known not only as the clinician-scientist who first developed and tested another big step in cancer treatment — monoclonal antibodies — but also as someone whose research and connections with other researchers worldwide puts him at the farthest edge of cancer treatment.

He didn’t disappoint with his talk. “There’s a lot more to be said about antibodies. I could go on a long time about them,” he said. “There are new generations, newly engineered versions — antibodies coupled to drugs, antibodies that are hooked to each other — there are all kinds of new stories to tell. But it’s T cells that have attracted the most excitement in the research field lately.”

Levy went on to describe various ways that researchers like Steve Rosenberg, MD, PhD, at the NIH; Zelig Eshhar, PhD, at the Weizmann Institute of Science; Carl H. June, MD, PhD, at the University of Pennsylvania; and Jim Allison, PhD, at the University of Texas MD Anderson Cancer Center, are engaging T cells, the most powerful soldiers of the immune system, to work against cancer.

“The new concept is targeting the immune system itself, getting it to re-educate itself and getting it to do its job when it’s not doing enough on its own,” Levy said. One approach, pursued by Allison, is to take the brakes off the immune system with an antibody against an immune system braking molecule called CTLA4. Other researchers in Japan and at Harvard and Yale have made an antibody to the “don’t kill me” signal that tumor cells use to protect themselves against the immune system.

The results of these new discoveries have, in many cases, already changed the standard of care, Levy said, giving many more patients with cancer much longer periods of response to treatment. Some of these new treatments come with serious autoimmune side effects — and scientists are working to figure out why some patients respond and others don’t, and why the treatments work with some cancers and not others, Levy said: “There are people working on this now all over the world.” At Stanford, he said, our team is testing a combination of radiation and low dose immunotherapy delivered directly to a tumor as a method that might reduce those side effects. Crystal Mackall, MD, who joined Stanford from NIH in January, is setting up “in a big way,” Levy said, to work on the technology that combines T cells with a virus that enables those killer immune cells to see and destroy what they ordinarily would be blind to.

“What if we put together all these therapies in smart ways? There are probably hundreds of clinical trials going on around the world, including 10 to 15 here at Stanford, that are trying to do exactly this,” he said. “The future is in combining these things — and the combinatorial possibilities are endless… Eventually, these immune therapies are going to take the place of our usual treatments. It’s going to change everything we do. I would say that those of us in the field of oncology are feeling the ground shaking under our feet right now.”

Levy’s words received resounding applause.

Levy's talk was part of the Edward Rubenstein Lecture series. In 2004, the first Edward Rubenstein lecturer was J. Michael Bishop, MD, who shared the 1989 Nobel Prize in Physiology or Medicine with Harold Varmus, MD, for the discovery of virus genes that can cause cancer in otherwise normal cells.

Previously: Stanford Medicine to join $250 million Parker Institute for Cancer ImmunotherapyImmunotherapy: New hope in treating cancer and Stanford's Ronald Levy offers peek at future of cancer therapy
Archived photo of Levy, which originally appeared in Stanford Medicine magazine, by Amanda Marsalis

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