Hematologist Joaquín Martínez (center in the first row) with his team from the H12O-CNIO Haematological Malignancies Clinical Research Unit and the Confocal Microscopy Unit led by Diego Megías (first left in the second row), which has also collaborated in the project. /Laura M. Lombardía. CNIO
The researchers developed a new cancer treatment, called CAR-NK-cell immunotherapy, which instead of T cells uses NK cells, which could be more effective and have fewer side effectsThis therapy could represent a substantial improvement over CAR-T immunotherapy, which represents a huge step forward in the treatment of blood cancer The researchers want to start conducting clinical trials at 12 de Octubre University Hospital as soon as possible
CAR-T cell immunotherapy is a huge step forward in the treatment of blood cancer. However, it can have serious side effects, so for the time being, it is a suitable option for some types of cancer only. Researchers from around the world are trying to improve it. A team at the H12O-CNIO Haematological Malignancies Clinical Research Unit, led by hematologist Joaquín Martínez, found that a similar treatment based on NK cells was more effective and had fewer side effects in mice with multiple myeloma, one of the most common types of blood cancer. Now the researchers want to start conducting clinical trials as soon as possible, as they are ready for this stage.
Their study appears in Blood Cancer Journal, a journal publishing articles related to haematological malignancies.
CAR-T-cell therapy, a type of treatment in which a patient’s T cells are modified in the laboratory so that they carry a chimeric antigen receptor (CAR), was approved only two years ago in Spain for patients with blood cancers such as acute lymphoblastic leukaemia and lymphomas that failed to respond to other therapies. This year, the European Medicines Agency greenlighted its use in patients with myeloma. It is thus a type of personalised therapy where the body’s own immunological defenders, the T cells, are genetically engineered to attack the tumour.
T cells are taken from the patient’s blood, then a gene for a special protein that binds to a specific molecule on the patient’s cancer cells is added to the T cells in the laboratory. These genetically modified CAR-T cells are grown in the laboratory and given back to the patient, binding to cancer cells and killing them.
The CNIO researchers focused on a receptor that binds to a different type of cells, the natural killer (NK) cells. CAR-immune cell therapy was developed with T cells because they are easier to handle than NK cells. However, CAR-NK cell therapies could be more effective and have fewer side effects.
In a mouse model of multiple myeloma, the team headed by Joaquín Martínez-López modified NK cells so that they could bind to the antigens of the NKG2D receptor (ULBP-1, ULBP-2, ULBP-3, ULBP-4, MICA AND MICB), which are normally not found in normal cells but is present in over 70 per cent of human cancers.
The study’s results were promising. The team found that CAR-engineered NK cells were able to detect and eliminate cancerous cells “very effectively”, as “25 per cent of the treated mice remained disease-free”.
“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 team hope they can start conducting clinical trials at 12 de Octubre University Hospital soon.
While over two hundred clinical trials focusing on CAR therapeutics are currently underway, the study carried out by the CNIO researchers is one of the few based on NK cells and one of the few publicly-funded CAR cell-based studies, whose cost is enormous and quite challenging for public health systems.
The study received funding from the CRIS Cancer Foundation, the Spanish Society of Haematology and the Carlos III Health Institute.
NKG2D-CAR-1 transduced natural killer cells efficiently target multiple myeloma. Leivas et al (Blood Cancer Journal, 2021). DOI: 10.1038/s41408-021-00537-w