New method uses nanoparticles to reprogram exhausted immune cells

A novel study led by Prof. Mira Barda-Saad and her research team at the Goodman Faculty of Life Sciences at Bar-Ilan University has unveiled a novel method to rejuvenate natural killer (NK) cells in the fight against cancer. The study addresses a critical challenge in cancer immunotherapy – NK cell exhaustion.

Recently it was discovered that the lymphocytes, either T cells or NK cells, including "engineered" NK cells, can become fatigued from continuously battling tumors and subsequently lose their function. To bypass this process, Prof. Barda-Saad's research team identified the underlying causes of NK cell dysfunction and developed a novel solution using nanoparticles to restore the vitality of these cells directly within the patient.

These nanoparticles, capable of targeting and silencing negative regulators, restore NK cell activity directly within the patient's body, bypassing the need for cell extraction and genetic modification.

NK cell dysfunction can occur in two ways: 1. During training, in which they undergo a training process in the immune system. If this process is disrupted, it can lead to NK cells that don't function correctly. 2. In the tumor microenvironment, when NK cells encounter a tumor, they are constantly stimulated.

Prof. Barda-Saad's group analyzed anergic and exhausted NK cells from both their training phase and tumor microenvironment, finding 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.

Image source: NIAID, Wikimedia Commons, CC BY-SA 4.0.