An experimental treatment that uses donor white blood cells to fend off cancer continues to show promise, early research in humans has found. The therapy appeared to be relatively safe and tolerable, and over half of patients with difficult-to-treat multiple myeloma responded to it.
T cells are one of the body’s most important defenders, able to recognize and kill off viruses, bacteria, parasites, and even cancer cells. Cancers employ a variety of strategies to evade these cells, but in recent years, scientists have developed new treatments that try to give the immune system a better fighting chance. One of these treatments is known as CAR T cell therapy, which genetically modifies someone’s T cells in the lab to turn them into more potent cancer killers. These therapies have had remarkable response rates for certain forms of previously untreatable cancer, as high as 90%.
The current method uses T cells derived from cancer patients themselves. As effective as it can be, it’s also costly and time-consuming, since the cells have to be cultivated and then grown en masse before they can be given back to the patient. Researchers at the Memorial Sloan Kettering Cancer Center and elsewhere have been working on a potential alternative: off-the-shelf CAR T cells derived from healthy donors. And they’re now conducting several Phase I trials of these cell products, known as allogeneic CAR T cells.
In a paper published Monday in Nature Medicine, the team detailed the latest results of their ongoing UNIVERSAL trial. They gave escalating doses of their CAR T cells to 43 patients with multiple myeloma, a form of cancer involving plasma cells. These patients’ cancers had either relapsed or stopped responding to other treatments. The team’s CAR T cells were not only modified to target these cancers in particular but also to lower the risk that they would attack the host body. And the patients were also given an antibody beforehand meant to weaken any immune response to the donor cells.
“The main takeaway is that an allogeneic CAR T cell therapy is feasible, has a reasonable safety profile, and can lead to durable remissions in patients with advanced multiple myeloma,” lead author Sham Mailankody, a physician and clinical director of Cellular Therapy Service at Memorial Sloan Kettering Cancer Center, told Gizmodo. “This is the very first trial of allogeneic CAR T cells in myeloma and therefore a significant milestone in the development of CAR T cell therapies in oncology.”
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Phase I trials are only the beginning of clinical research. And despite the potential of allogeneic CAR T cell therapy, it’s proven harder to make it a viable reality compared to the current standard. A key challenge with these treatments, Mailankody notes, is being able to overcome the host’s immune response well enough to let these cells grow and survive so that they can fight the cancer. And while a slight majority of patients did initially respond to their treatment (55%), the lack of response in many leaves plenty of room for improvement. It will also take time to measure the durability of these treatments and which cancers they might be best suited for. The exact costs of allogeneic CAR T cell therapy aren’t known either yet, though the team hopes it will be less expensive than the current model.
But with these early findings, the researchers are optimistic about the future of their treatment and similar ones in development. In the ongoing UNIVERSAL trial, they’re planning to test several strategies to improve the effectiveness of this specific treatment. And elsewhere, they’re developing other allogeneic and more traditional CAR T cell therapies.
