Israeli nanoparticles revitalize exhausted immune cells in the fight against cancer
Israeli researchers unveiled a technique using nanoparticles to rejuvenate certain white blood cells, an innovation that could revolutionize cancer treatment.
Bar-Ilan University Photo: Yossi Zeliger/TPS-IL
Natural killer cells are a type of white blood cell vital to the body’s immune defense, tasked with identifying and destroying cancerous and viral-infected cells. These cells are called “natural killers” because — unlike other immune cells that require activation or the presence of antibodies — they can recognize and destroy certain harmful cells without needing prior exposure or specific recognition signals.
In recent years, cancer treatment has increasingly relied on immunotherapy strategies, such as extracting immune cells from a patient, genetically modifying them in a laboratory to enhance their ability to target cancer, and then reintroducing these enhanced cells back into the patient’s body.
However, a phenomenon known as immune cell exhaustion which affects the “natural killer cells” has emerged as a significant obstacle to that approach. After prolonged engagement with tumour cells, the NK cells become fatigued, and their ability to fight cancer declines.
A team of researchers at Bar-Ilan University in Ramat Gan led by Prof. Mira Barda-Saad focused on rejuvenating the NK cells. The study, recently published in the peer-reviewed The EMBO Journal, found that nanoparticles could restore the vitality of the NK cells directly within the patient, eliminating the need for the complex process of cell extraction and genetic modification.
Barda-Saad told The Press Service of Israel that the nanoparticle technique, called Chimeric Antigen Receptor (CAR), had a success rate of “40-50% depending on the type of cancer being treated.”
The researchers pinpointed two key factors that contribute to NK cell dysfunction: the enzyme DGK alpha and the transcription factor Egr2. These factors are implicated in both the exhaustive state, where overstimulated NK cells become slow to respond, and the anergic state, where NK cells become unresponsive.
Through analysis of the NK cells in their different phases, the researchers discovered that the dysfunction in these cells could be reversed. This was achieved by introducing nanoparticles specifically targeting and silencing the DGK alpha enzyme and Egr2 transcription factor. This essentially revitalized the exhausted NK cells which resumed their role in attacking and killing cancer cells.
The effectiveness of this approach was demonstrated in both three-dimensional tissue cultures and experiments with mice. The results were particularly promising in cases of aggressive pancreatic cancer, a notoriously difficult-to-treat form of the disease.
With the research now published, Barda-Saad told TPS-IL that the nanoparticle treatment is years away from coming into use. “The next step is actually to introduce it to pharmacological companies, to pharma, and to try to raise money and to do some clinical trials.”
