*March 2025*
Cell-based immunotherapies such as chimeric antigen receptor T cells (CAR-T) have transformed cancer care in recent years, dramatically improving the treatment of blood cancers in particular.
But traditional autologous CAR-T therapy has some drawbacks that may limit how many patients it can help. Harvesting, engineering and readministering a person’s own T cells calls for a patient-specific, personalized manufacturing process, which can be time-consuming and expensive — leading to delays in critical treatment. A new approach using a different type of immune cell, however, offers promise in expanding cellular immunotherapy applications to treat more types of cancer, and broader target populations with an off-the-shelf option that’s not patient specific.
Natural killer cells are another type of lymphocyte that can destroy pathogens and abnormal cells without prior exposure to them. “Natural killers are a really useful cell that goes around mopping up other abnormal cells,” says Bill Shingleton, head of cell therapy R&D at life sciences company Cytiva. “They shoot from the hip if they don’t recognize something. So, they’re a good cell if you want therapeutic benefit, particularly against tumour cells.”
A killer combination
When combined with CARs, the natural killer (NK) cells can also be trained to target specific cancers, with several unique features that give CAR-NK a potential advantage over CAR-T therapy.
Where manufacturing autologous CAR-T cell therapies poses challenges such as prolonged turnaround times and managing patient-specific materials, CAR-NKs are more receptive to allogeneic formulations derived from donor cells. “We can identify a healthy donor, isolate their NKs and then culture these to a much larger scale. Eventually, we can use that same healthy patient’s material to dose multiple different patients in the clinic,” explains Sanket Dahotre, senior manager for cell therapy process development at GeneFab, a contract development and manufacturing company in San Francisco, California.
NK cells are good candidates for allogeneic treatments because they’re considered unlikely to trigger potentially dangerous immunogenic reactions — such as a cytokine response or graft versus host disease — when there’s a human leukocyte antigen mismatch between recipient cells and drug products made from donor cells.
While it’s also possible to make an autologous patient-specific therapy from NK cells, Shingleton doesn’t see that idea taking off. “Beating the efficacy of CAR-T would be tough,” he says. CAR-NK’s advantage is instead in its potential to simplify the logistics of cell therapy, providing the promise of a universal off-the-shelf immunotherapy. Read more.
