Prof. Mira Barda-Saad from the Goodman Faculty of Life Sciences, Bar Ilan University. Photo courtesy of BIU
Nanoparticles can revive exhausted cancer-fighting immune cells
Natural killer cells, essential for fighting cancer, often malfunction due to exhaustion. A promising new technique could rejuvenate them.
It’s not just our minds and bodies that get exhausted when battling cancer, it’s also the natural killer (NK) cells of our bodies – a key component of the immune system – that get fatigued and lose function when they have to keep fighting the disease.
Now, a new study at Bar-Ilan University offers a novel method to rejuvenate NK cells using nanoparticles, restoring their vitality to give them the strength to keep fighting cancer cells.
Cancer is the second leading cause of death in the United States, after heart disease. In 2024, the American Cancer Society estimates that there will be two million new cancer cases in the country – around 5,480 new diagnoses every day.
NK cells are a key component of the immune system, and are crucial for identifying and destroying cancerous and viral cells.
In recent years, doctors have begun working with immunotherapeutic strategies, such as the Chimeric Antigen Receptor (CAR) approach, to extract patient cells, modify them genetically in a laboratory to enhance their ability to combat cancer cells, and then reintroduce them into the body.
New research has shown, however, that the lymphocytes – either T cells or NK cells, including the engineered NK cells – can become fatigued from continuously battling tumors and subsequently lose their function.
To bypass this process, Prof. Mira Barda-Saad and a team of researchers at the Goodman Faculty of Life Sciences identified the underlying causes of NK cell dysfunction and developed a novel solution.
They use nanoparticles that target and silence negative regulators and restore NK cell activity directly within the patient’s body, bypassing the need for cell extraction and genetic modification.
Revitalizing natural killer cells
According to the researchers, NK cell dysfunction occurs in two ways. The first is during the “training process” in the immune system. If this process is disrupted and they receive inappropriate signals, it can lead to “anergic” NK cells that don’t function correctly.
The second is in the tumor microenvironment. When NK cells encounter a tumor, they are constantly stimulated. If this stimulation is excessive and prolonged, it can lead to exhaustion where the NK cells become less effective at fighting cancer.
Barda-Saad’s group analyzed anergic and exhausted NK cells from both their training phase and tumor microenvironment, and found that they are similarly dysfunctional. They identified two key factors contributing to this dysfunction: the enzyme DGK alpha and the transcription factor Egr2.
“Experiments in three-dimensional tissue culture and in-vivo mice models have shown that nanoparticles, acting as a platform for drug delivery, can reprogram the dysfunctional natural killer cell population,” said Barda-Saad.
“After the research group introduced nanoparticles that silence the two negative regulators, the killer cells returned to their normal function and efficiently killed cancer cells.”
These promising findings, obtained in animal models bearing aggressive pancreatic cancer, could pave the way for the development of effective treatments against solid tumors using an immunotherapeutic strategy, offering hope to patients and professionals in the field.
The study was published recently on the cover of The EMBO Journal.
