14 October 2021

A new blood cancer treatment has been developed for multiple myeloma that could be more effective than existing therapies and lead to fewer side effects.

The CAR-NK cell immunotherapy, only tested in mice so far, is similar to CAR-T cell therapies currently available for blood cancers, however it uses NK cells instead of T cells. Spanish researchers at the H12O-CNIO Haematological Malignancies Clinical Research Unit say their CAR-NK cell therapy shows promise in their mouse models, and that they are ready for human trials.

The team, led by haematologist Joaquín Martínez-López, modified NK cells from myeloma patients so that they produced a chimeric antigen receptor (CAR) that was based upon the NKG2D receptor. This meant that the activated and expanded NK cells could bind to ligands of the NKG2D receptor (ULBP-1, ULBP-2, ULBP-3, ULBP-4, MICA AND MICB), which are usually not found in normal cells but are present on more than 70% of human cancers.

The researchers showed their CAR-NK cells could kill multiple myeloma cells lines in the lab and in mice. They found that CAR-NK cells detected and eliminated cancerous cells “very effectively” and that 25% of the treated mice remained disease-free. What’s more, the CAR‑NK cells were more effective against the multiple myeloma cell lines than CAR‑T cells, and mice had fewer side effects. The CNIO team are now hoping to start clinical trials as soon as possible.

Martínez-López said: “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.”


Source:

Leivas A, Valeri A, Córdoba L, García-Ortiz A, Ortiz A, Sánchez-Vega L, Graña-Castro O, Fernández L, Carreño-Tarragona G, Pérez M, Megías D, Paciello ML, Sánchez-Pina J, Pérez-Martínez A, Lee DA, Powell DJ Jr, Río P, Martínez-López J. (2021) “NKG2D-CAR-transduced natural killer cells efficiently target multiple myeloma.” Blood Cancer Journal, doi: 10.1038/s41408-021-00537-w

Link: https://www.nature.com/articles/s41408-021-00537-w

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