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A new therapy for acute lymphoblastic leukemia, a swift-growing cancer that kills more than 60 percent of those afflicted, is based on extracting T cells and modifying them to home in on and destroy B cells in healthy and cancerous tissue.

Lymphoblastic leukemia has show to be very hard to treat up until now, with a high death toll, this form of leukemia can often resist conventional chemotherapies. A recent small study suggests that genetically modified immune cells can not only drive the cancer into remission, but clear it out of the patients bodies completely.

The trial was done in five patients so far, testing a new “fringe” therapy for lymphoblastic leukemia, and the results published in Science Translational Medicine, end of March. The trial was a successes, forcing the cancer into submission in 4 out of 5 patients.

The novel therapy is based on extracting immune cells called T cells from a patient, genetically modify them, and then reinfuse them back. For this purpose, the T cells were engineered to express a receptor for a protein on other immune cells, known as B cells, found in healthy and cancerous tissue. The B cells were then to be destroyed by the modified T cells, and although patients can live without B cells, cancers are completely eradicated.

Once reintroduced into the patients, the tricked T cells quickly homed in on their targets and eradicated them completely. “All of our patients very rapidly cleared the tumor,” said Michel Sadelain, a researcher at the Memorial Sloan-Kettering Cancer Center in New York and an author of the study. He says that he treatment “worked much faster than we thought”.

The technique has already been tested and shown promise against chronic leukemia, but there were considerable doubts about whether it could tackle the faster-growing acute lymphoblastic leukemia, a tenacious disease that kills more than 60% of those afflicted.

Carl June, an immunologist at the University of Pennsylvania in Philadelphia and a pioneer in engineering T cells to fight cancer, stated that he is surprised that the method worked so well against such a swift-growing cancer. The next step, he says, is to move the technique into clinical centers, and out of academic research in universities, and make it more available for a broader range of patients.

“What needs to be done is to convince oncologists and cancer biologists that this new kind of immunotherapy can work,” – said Karl June.

One of the patients involved in this trial was a 58-year-old man, who had just passed a series of high dose chemotherapy. The chemotherapy showed no effect, and after suffering the side effects and pains involved in chemotherapy, the man was left with no results, in a state of despair. Over 70% of his bone marrow was already tumor tissue. So the last hope was this new therapy.

Brentjens, oncologist, also at Memorial Sloan-Kettering Cancer Center, Sadelain and their colleagues then extracted T cells from the patient and re-engineered them to express a ‘chimeric antigen receptor’, or CAR, that would target cells expressing a protein called CD19. Because CD19 is found on both healthy and cancerous B cells, the engineered T cells were unable to distinguish between the two. However, patients can live without B cells.

Two weeks after the procedure, the patient was showing considerable signs of improvement. The treatment had driven the cancer into remission — as it did for the other four patients in the trial — so he became eligible for a bone-marrow transplant, which, in fact, saved his life. A hundred days later, he is doing well, says Brentjens. Four of the five patients were well enough to receive transplants; the remaining patient relapsed and was ineligible.

Pharmaceutical firms have tended to be wary of the CAR technique, and avoid it, because it is technically challenging, must be personalized to the patient, thus presenting a low profit opportunity, and faces an untested path to regulatory approval, beginning at clinical trials, as said by Steven Rosenberg, head of the tumor immunology section at the National Cancer Institute in Bethesda, Maryland.

But this has the potential to change. Rosenberg points to a collaboration formed in August last year between June's group and the drug giant Novartis, as well as the launch of several small CAR-focused biotechnology firms. And Sadelein says that he is currently an investigator on a trial with the Dana-Farber Cancer Institute in Boston, Massachusetts, to test whether the technique can be exported to other treatment centers, and perhaps be extended to other types of cancer, among other outcomes.


Results of this study were published in Science Translational Medicine, March 30th