One stem cell generates 14 million tumor-killing NK cells in major cancer breakthrough
Researchers have developed a new, more efficient method for generating natural killer (NK) cells for cancer immunotherapy. This advancement addresses key challenges in current approaches, potentially paving the way for more accessible and affordable cancer treatments.
Harnessing the Power of NK Cells
NK cells are crucial components of the body’s immune system, providing an early defence against viruses and cancer. Their ability to identify and destroy abnormal cells makes them a promising tool in cancer treatment. Scientists are utilizing this potential through chimeric antigen receptor (CAR)-NK therapy, which involves equipping NK cells with engineered receptors to target and eliminate cancer cells with greater precision.
Overcoming Limitations of Traditional Methods
Traditional methods of producing CAR-NK cells rely on mature NK cells sourced from peripheral blood or cord blood. However, these methods face significant hurdles, including inconsistencies between cells, difficulties in genetic modification, high production costs, and lengthy preparation times. The team, led by Prof. WANG Jinyong at the Institute of Zoology of the Chinese Academy of Sciences, sought to overcome these limitations.
A New Approach: Starting with Stem Cells
Instead of modifying mature NK cells, the researchers began with CD34+ hematopoietic stem and progenitor cells (HSPCs) derived from cord blood. They then generated induced NK (iNK) cells and CAR-engineered iNK (CAR-iNK) cells. This strategy involved shifting the genetic engineering process earlier in the cell’s development, directly at the CD34+ HSPC stage, combining CAR transduction with strong expansion and guided development into NK cells.
A Three-Step Process for Cell Production
The team employed a three-stage system to expand and differentiate the cells. First, CD34+ HSPCs (or CD19 CAR-transduced HSPCs) were expanded using irradiated AFT024 feeder cells, resulting in an 800- to 1,000-fold increase in cell numbers within 14 days. Next, the expanded cells were cultured with OP9 feeder cells to create structures that support NK cell development. Finally, the cells matured and multiplied, yielding highly pure iNK or CAR-iNK cells expressing endogenous CD16.
The findings were published in Nature Biomedical Engineering.
Reduced Costs and Improved Efficiency
This new method dramatically reduces the amount of viral vector needed for CAR engineering. Compared to traditional methods, it used approximately 1/140,000 to 1/600,000 as much viral vector. The researchers state that this approach not only improves the efficiency of producing iNK and CAR-iNK cells but also significantly lowers the cost of CAR engineering.
Promising Results in Leukemia Models
Laboratory tests demonstrated the potent tumor-killing ability of both iNK and CAR-iNK cells. In mouse models of human B-cell acute lymphoblastic leukemia (B-ALL), CD19 CAR-iNK cells reduced tumor growth and extended survival.
Frequently Asked Questions
What are NK cells?
NK cells are a type of immune cell that plays a critical role in the body’s early defence against viruses and cancer.
What is CAR-NK therapy?
CAR-NK therapy involves equipping NK cells with a lab-designed receptor (a CAR) to recognize a specific marker on cancer cells and attack them more precisely.
What is the main advantage of this new method?
This new method starts with CD34+ hematopoietic stem and progenitor cells from cord blood, leading to a more efficient and cost-effective production of iNK and CAR-iNK cells.
As research continues, this new method could lead to more widely available and affordable cancer immunotherapies, but further studies will be needed to determine its effectiveness and safety in humans.