Develop ‘Utterly Transformative’ Gene Therapies

The approval of gene therapy for leukemia, expected in the next few months, will open the door to a radically new class of cancer treatments.

Companies and universities are racing to develop these new therapies, which re-engineer and turbocharge millions of a patient’s own immune cells, turning them into cancer killers that researchers call a “living drug.” One of the big goals now is to get them to work for many other cancers, including those of the breast, prostate, ovary, lung and pancreas.

“This has been utterly transformative in blood cancers,” said Dr. Stephan Grupp, director of the cancer immunotherapy program at the Children’s Hospital of Philadelphia, a professor of pediatrics at the University of Pennsylvania and a leader of major studies. “If it can start to work in solid tumors, it will be utterly transformative for the whole field.”

But it will take time to find that out, he said, at least five years.

This type of treatment is now also being studied in glioblastoma, the aggressive brain tumor that Senator John McCain was found to have this week. Results of a study at the University of Pennsylvania, published Wednesday, were mixed. In the first 10 patients treated there, one has lived more than 18 months with what the researchers called “stable disease.” Two other survivors have cancer that has progressed, and the rest have died.

Studies are forging ahead on many fronts. Researchers plan to try giving the cell treatment to children with earlier stages of leukemia than in the past, combining it with other treatments and developing new types of cell therapy. One new version, with human trials just starting, uses immune cells extracted not from the patient, but from samples of umbilical-cord blood donated by mothers when they give birth

The products closest to approval so far have a limited focus — to treat blood cancers like leukemia (for which an F.D.A. advisory panel recommended approval of the first treatment last week) and lymphoma, as opposed to the solid tumors that form in organs like the breasts and lungs and cause many more deaths. About 80,000 people a year have the kinds of blood cancers that the first round of new treatments can fight, out of the 1.7 million cases of cancer diagnosed annually in the United States

The new leukemia treatment involves removing millions of white blood cells called T cells — often referred to as the soldiers of the immune system — from the patient’s bloodstream, genetically engineering them to recognize and kill cancer, multiplying them and then infusing them back into the patient. The process is expensive because each treatment has to be made separately for each person.

Solid tumors are less amenable to treatment with these altered cells — which scientists call CAR-T cells — but studies at various centers are trying to find ways to use it against mesothelioma and cancers of the ovary, breast, prostate, pancreas and lung.

“These solid tumors are like Fort Knox,” Dr. Grupp said. “They don’t want to let the T cells in. We need combination approaches, CAR-T plus something else, but until the something else is defined we’re not doing to see the same kind of responses.”

The pioneering T-cell therapy for leukemia was created at the University of Pennsylvania, which licensed it to Novartis. The F.D.A. panel recommended approval of it for a narrow subset of severely ill patients, only a few hundred a year in the United States: those ages 3 to 25 who have B-cell acute lymphoblastic leukemia that has relapsed or not responded to the standard treatments. Those patients have poor odds of surviving, but in clinical trials, a single T-cell treatment has produced long remissions in many and possibly even cured some.

Novartis plans to request another approval later this year of the same treatment (which it calls CTL019 or tisagenlecleucel) for adults who have a type of lymphoma — diffuse large B-cell lymphoma that has relapsed or resisted treatment. A competitor, Kite Pharma, has also filed for approval of a T-cell treatment for lymphoma. Another competitor, Juno, suffered a setback when it shut down a T-cell study in adults after five patients died from brain swelling. Kite has also reported one such death.

Novartis is studying several other types of T-cells, with different genetic tweaks, to treat chronic lymphocytic leukemia, multiple myeloma as well as glioblastoma.

Some of the more promising work so far involves efforts to make the existing gene treatments even more effective in blood cancers. For lymphoma patients, the T cells are being given along with a drug, ibrutinib, and the combination seems to work better than either treatment alone