Innovative Engineered CAR-NK Cells Show Promise in Evasion of Immune Rejection and Enhanced Cancer Targeting

Scientists from MIT and Harvard Medical School have developed a groundbreaking method to engineer CAR-NK (Chimeric Antigen Receptor-Natural Killer) cells that can better evade the immune system's defenses and more effectively target cancer cells. These immune cells, similar to the widely studied CAR-T cells, are reprogrammed to recognize and attack tumor cells, but a significant hurdle has been their rejection by the host immune response.

The new approach involves customizing CAR-NK cells to minimize their visibility to the patient’s immune system, specifically by reducing surface proteins called HLA class I proteins that normally trigger immune rejection. The researchers achieved this by engineering the cells to express short interfering RNA (siRNA) sequences to silence these proteins, while also introducing genes for proteins like PD-L1 or single-chain HLA-E (SCE) that bolster the NK cells’ ability to kill cancer cells.

In preclinical studies with mice possessing human-like immune systems, these modified CAR-NK cells demonstrated a remarkable ability to survive longer and nearly eradicate lymphoma tumors, outperforming unmodified or only CAR-expressing NK cells. Moreover, they showed a lower propensity to cause cytokine release syndrome, a dangerous side effect associated with immunotherapies.

This advancement paves the way for the development of off-the-shelf, ready-to-use CAR-NK therapies that can be administered immediately upon diagnosis, reducing the time and complexity associated with current personalized treatments. The team's work suggests that these CAR-NK cells could serve as a safer, more versatile alternative to CAR-T cells and may be adapted for treating various cancers, autoimmune diseases, and other conditions.

By enabling immune-evasive properties in NK cells, this research opens new horizons in cancer immunotherapy, promising more effective and accessible treatments in the near future.

Source: https://medicalxpress.com/news/2025-10-car-nk-cells-evade-immune.html