Optimized costimulatory domains boost tumor killing in CAR NK cells

Researchers are exploring new ways to enhance the effectiveness of CAR-NK cell therapy, a promising approach to cancer treatment. A study conducted at the Ribeirão Preto Blood Center and the Center for Cell-Based Therapy (CTC) investigated how specific components within chimeric antigen receptors (CARs) impact the ability of these cells to destroy tumors.

Boosting the Attack: The Role of 2B4 and DAP12

The research focused on CARs incorporating the 2B4 and DAP12 costimulatory domains. Tests revealed that these components help prepare the NK cells to attack, ultimately increasing their tumor-killing capabilities. The findings were published in the journal Frontiers in Immunology.

Did You Know? The Center for Cell-Based Therapy (CTC) is one of the Research, Innovation, and Dissemination Centers (RIDCs) supported by FAPESP and is linked to the general and teaching hospital of the Ribeirão Preto Medical School of the University of São Paulo.

CAR-NK Therapy: A Revolution in Cancer Treatment

CAR-based cell therapies are transforming cancer treatment, particularly for blood cancers. While significant progress has been made in understanding what works best in CAR-T cells, questions remain regarding the optimal intracellular signals for CAR-NK cells.

Combining Stimulation and Control

The CTC’s research suggests that combining optimized costimulation with reversible pharmacological control can improve the potency and efficiency of CAR-NK therapies. This approach could lead to the development of more effective cell-based treatments.

Expert Insight: This research highlights the ongoing effort to refine CAR-NK therapy, building on successes seen with CAR-T cells while addressing the unique characteristics of natural killer cells. The focus on both enhancing activation and maintaining control represents a sophisticated approach to maximizing therapeutic benefit.

Researchers also evaluated the use of the drug dasatinib to temporarily control the activation of these cells. In animal models, CAR-NK cells with 2B4-DAP12, when pretreated with dasatinib, demonstrated improved tumor control compared to traditional CAR-NK cell versions.

Frequently Asked Questions

What is a CAR?

A CAR, or chimeric antigen receptor, is a synthetic receptor engineered to express on immune cells, like NK cells, to target specific antigens on cancer cells.

What is the role of costimulatory domains like 2B4 and DAP12?

2B4 and DAP12 are costimulatory domains that help “ready” the NK cells to attack and increase their ability to destroy tumors.

What is dasatinib and how was it used in this research?

Dasatinib is a drug that was used to temporarily control the activation of CAR-NK cells. In animal models, CAR-NK cells pretreated with dasatinib showed better tumor control.

What impact might further refinement of CAR-NK therapies have on the future of cancer treatment?