Researchers Develop Method to Supercharge Cancer-Killing Immune Cells

Researchers at the Ribeirão Preto Blood Center and Center for Cell-Based Therapy in Brazil have developed an enhanced approach to cancer immunotherapy by engineering natural killer cells with chimeric antigen receptors containing 2B4 and DAP12 costimulatory components. The modified CAR-NK cells showed significantly improved ability to destroy tumor cells and control tumor growth in animal models compared to traditional versions. The team also tested dasatinib, a drug that can temporarily suppress cell activity, to create controllable pauses that may improve both safety and efficiency of the therapy. The study, published in Frontiers in Immunology, demonstrates how combining optimized activation signals with reversible pharmacological control could lead to more advanced and controllable cell-based cancer treatments.

Engineering NK cells with enhanced CAR designs

• ▪The study on enhanced chimeric antigen receptors for natural killer cells was published in Frontiers in Immunology.
• ▪Incorporating 2B4 and DAP12 into chimeric antigen receptor design enhanced natural killer cells' activation state, making the cells more effective at targeting tumors.
• ▪The chimeric antigen receptors (CARs) tested by researchers at the Ribeirão Preto Blood Center included specific costimulatory components such as 2B4 and DAP12.
• ▪The addition of 2B4 and DAP12 costimulatory components to chimeric antigen receptors made natural killer cells ready to attack and significantly improved their ability to destroy tumor cells.
• ▪Researchers at the Ribeirão Preto Blood Center and the Center for Cell-Based Therapy (CTC) in Brazil used the NK-92 cell line to test new designs of chimeric antigen receptors (CARs).

Drug-based control strategy using dasatinib

• ▪Researchers at the Ribeirão Preto Blood Center tested dasatinib, a drug that can briefly suppress cell activity, to see how controlled pauses might affect natural killer cell performance.
• ▪Combining optimized activation signals with reversible pharmacological control can improve both the strength and efficiency of CAR-NK therapies.
• ▪The drug-based control approach using dasatinib may help researchers design more advanced and controllable cell-based cancer treatments in the future.

Preclinical results and institutional collaboration

• ▪The Center for Cell-Based Therapy (CTC) is one of the Research, Innovation, and Dissemination Centers (RIDCs) supported by FAPESP.
• ▪The Center for Cell-Based Therapy (CTC) operates within the Ribeirão Preto Blood Center.
• ▪The Center for Cell-Based Therapy (CTC) is affiliated with the general and teaching hospital (Hospital das Clínicas) of the Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP).
• ▪CAR-NK cells engineered with 2B4-DAP12 and pretreated with dasatinib were better at controlling tumor growth in animal models compared to more traditional versions of the therapy.

Perspective of Researchers at the Ribeirão Preto Blood Center and Center for Cell-Based Therapy

• ▪The combination of 2B4 and DAP12 costimulatory components represents a novel approach to engineering more potent natural killer cells for cancer treatment.
• ▪Using dasatinib to create controlled pauses in natural killer cell activity could address safety concerns associated with overly aggressive immune responses in CAR-based therapies.
• ▪The enhanced CAR-NK cell design developed at the Ribeirão Preto Blood Center may offer advantages over traditional CAR-T cell therapies in terms of controllability and tumor targeting.

Perspective of Cancer immunotherapy researchers and clinicians

• ▪The ability to pharmacologically control engineered immune cells addresses a major challenge in CAR-based therapies where uncontrolled activation can cause severe side effects.
• ▪Natural killer cell-based immunotherapies have potential advantages over T cell-based approaches because NK cells can recognize and attack tumors without requiring patient-specific customization.

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