Researchers in Spain believe that a new type of CAR therapy using natural killer cells, could be more effective and have fewer side effects in treating blood cancers like multiple myeloma than CAR T cell therapy.
CAR T cell therapy is a growing field of myeloma research, but it can come with significant side effects like cytokine release syndrome (CRS) and neurotoxicities. Researchers are looking for both ways to improve CAR T therapies and to develop new approaches that may be equally good with fewer toxicities.
Spanish researchers of the H12O-CNIO Haematological Malignancies Clinical Research Unit, led by hematologist Joaquín Martínez, found that a similar CAR treatment using natural killer cells (NK cells) instead of T cells was more effective and had fewer side effects in mice with multiple myeloma. Early in-human trials are now planned.
The researchers hypothesized that CAR-NK cells could be less toxic when targeting resistant myeloma cells. In their study, they analyzed the anti-tumor activity of activated and expanded NK cells (NKAE) and CD45RA- T cells from multiple myeloma patients that were engineered to express an NKG2D-based CAR that target antigens of the NKG2D receptor, which are not typically found on normal cells but are present in over 70% of human cancers.
“Overall, our results show that it is possible to modify autologous NK cells from multiple myeloma patients to safely express a NKG2D-CAR. These cells […] could be an effective strategy against multiple myeloma”, says Martínez-López.
The study results showed that although memory T cells were more stably converted, the CAR NK cells had greater killing power towards the myeloma cells while showing minimal activity against healthy cells. In mouse models, 25% of the mice remained disease free. Overall, the study showed that it is possible to modify a myeloma patient's own NK cells to create a CAR therapy.
The researchers hope they can begin an in-human clinical trial at the 12 de Octubre University Hospital in Spain soon.