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NYT Syndicate
The approval of gene therapy for leukaemia, 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 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 programme at the Children's Hospital of Philadelphia, a professor of paediatrics at the University of Pennsylvania and a leader of major studies."If it can start to work in solid tumours, 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 also being studied in glioblastoma, the aggressive brain tumour that Sen John McCain was found to have. Results of a study at the University of Pennsylvania were mixed. In the first 10 patients treated, 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 have a limited focus ” to treat blood cancers like leukemia (for which an FDA advisory panel recommended approval of the first treatment last week) and lymphoma, as opposed to the solid tumours 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 treatments are expected to cost hundreds of thousands of dollars, and they come with risks. Patients in the earliest studies nearly died from side effects like raging fever, low blood pressure and lung congestion. Doctors have learned how to control those reactions, but experts also have concerns about possible long-term effects like second cancers that could in theory be caused by the disabled viruses used in genetic engineering. No such cancers have been seen so far, but it is too soon to rule them out.
The new leukaemia 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 recognise 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 tumours are less amenable to treatment with these altered cells ” which scientists call CAR-T cells ” but studies at various centres are trying to find ways to use it against mesothelioma and cancers of the ovary, breast, prostate, pancreas and lung.
"These solid tumours are like Fort Knox," 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 leukaemia was created at the University of Pennsylvania, which licensed it to Novartis. The FDA 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 3-25 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.
Studies in children are also underway to combine T-cell treatment with the immunotherapy drugs called checkpoint inhibitors, which help unleash the cancer-killing power of T-cells. There will be many such studies, Grupp predicted, but, he said,"It's early days."
The T-cells in the Novartis products, and in the earliest ones its competitors are developing, have been engineered to seek and destroy cells that display on their surfaces a protein called CD19 ” a characteristic of many leukaemia and lymphomas.
Identifying other targets would be a boon, Grupp said, because sometimes leukaemic cells lacking CD19 proliferate, escape the treatment and cause relapse.
Another target is being studied, and Grupp said the next step, which he called"super important," would be to attack two cellular targets in the same patient.
In the next year or so, he said, that approach will also be studied in both children and adults who have acute myeloid leukaemia, which he described as a"tough disease."
