Brazilian researchers are advancing a promising cancer immunotherapy by making natural killer (NK) cells more powerful and precise. In a recent study, scientists at the Ribeirão Preto Blood Center and Cell Therapy Center (CTC) used the NK-92 cell line to test a new design of a chimeric antigen receptor (CAR). These engineered receptors contain specific co-stimulatory components such as 2B4 and DAP12 that help activate cells. The study results showed that these additions made the cells “attack-ready” and significantly increased their ability to destroy tumor cells. This research Frontiers of immunology.
CAR-based therapies are already transforming the treatment of blood-related cancers in particular. Although CAR-T cells are well-studied, scientists are still working to understand how to optimize CAR-NK cells. One of the key challenges is to identify which internal signaling mechanisms allow these cells to perform best.
New research is addressing this gap by focusing on how specific signaling domains influence NK cell activity. By incorporating 2B4 and DAP12 into the CAR design, the researchers were able to enhance the activation state of the cells and target tumors more effectively.
Combination of activation signals and drug control
The research team also explored strategies to fine-tune cells using temporary drug-based approaches. They tested dasatinib, a drug that can temporarily suppress cellular activity, to see how controlled pauses affected performance.
Their results suggest that both the intensity and efficiency of CAR-NK therapy can be improved by combining an optimized activation signal with reversible pharmacological control. This approach could help researchers design more advanced and controllable cell-based cancer treatments in the future.
Stronger tumor control in preclinical models
According to the press office of the Ribeirão Preto Blood Center, experiments in animal models have shown promising results. CAR-NK cells engineered with 2B4-DAP12 and pretreated with dasatinib had better control of tumor growth compared to conventional treatments.
Research cooperation and institutional support
The Center for Cell-Based Therapy (CTC) is one of the Research, Innovation, and Dissemination Centers (RIDCs) supported by FAPESP. The Hospital operates within the Ribeirão Preto Blood Center and is affiliated with the General and Teaching Hospital of the Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP) (the “Hospital”).
Taken together, these findings point to a new generation of CAR-NK therapies that can provide a more powerful and adaptable way to fight cancer.

