An Update on Trialing Engineered T Cells Against Leukemia

Following on from research noted last year:

Genetically engineered immune cells can drive an aggressive type of leukaemia into retreat, a small clinical trial suggests. The results of the trial - done in five patients with acute lymphoblastic leukaemia - [represent] the latest success for a 'fringe' therapy in which a type of immune cell called T cells are extracted from a patient, genetically modified, and then reinfused back. In this case, the T cells were engineered to express a receptor for a protein on other immune cells, known as B cells, found in both healthy and cancerous tissue.

"All of our patients very rapidly cleared the tumour. The treatment worked much faster than we thought." The next step [is] to move the technique out of the 'boutique' academic cancer centres that developed it and into multicentre clinical trials. "What needs to be done is to convince oncologists and cancer biologists that this new kind of immunotherapy can work."

[A researcher] remembers the day that he had to tell one of the patients in the trial that the weeks of high-dose chemotherapy the 58-year-old man had endured had not worked after all. "It was painful to have that conversation. He tells me now it was the worst news he has ever heard in his life." Another month in the hospital on intensive chemotherapy drugs did nothing to help. By the time the man started the trial, 70% of his bone marrow was tumour.

[Researchers] then extracted T cells from the patient and 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 discriminate between the two. However, patients can live without B cells.

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



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