A new technology developed at Bar-Ilan University (BIU) makes possible the use of nanoparticles to help the body’s own immune system fight cancer. A nanoparticle, ranging between one to 100 nanometers in size, can exhibit significantly different physical and chemical properties compared to their larger material counterparts. A nanometer is equal to a billionth of a meter.
The discovery eliminates obstacles in the environment of the malignant tumor that hinder the normal activity of natural killer (NK) cells – a special sub-type of white blood cells called lymphocytes. The research has just been published in the journal EMBO Molecular Medicine under the title “Modulation of intrinsic inhibitory checkpoints using nanocarriers to unleash NK-cell activity.”
Natural killer cells are a potent defense weapon of the body that helps the immune system in its fight against viral infections, tumor growth and the spread of cancerous metastases (spreading). Cancer researchers have known for some time that NK-cells have important potential to treat cancer by immunotherapy since they have the ability, under certain circumstances, to readily and efficiently attack cancer cells and kill them directly.
“The use of nanoparticles in this innovative and groundbreaking domain of next-generation immunotherapeutic drugs enhances the immune response against pathogens that cause illness
Prof. Mira Barda-Saad
NK-cells can produce a potent immune response in the vicinity of the tumor, known as the tumor micro-environment (TME). But despite their great promise, several obstacles make it difficult for researchers and physicians to use them for immunotherapy, including the need to manipulate them using molecular/genetic engineering outside the body to enhance their therapeutic efficacy against cancer. In addition, no clinical study has yet proved that NK-cell based treatments are effective in patients with advanced cancer because the TME usually activates inhibitory mechanisms that suppress their activity.
Research ingenuity
TO OVERCOME these obstacles, Prof. Mira Barda-Saad and her research team at BIU’s Goodman Faculty of Life Sciences developed a mechanism to introduce lipid-based nanoparticles into the NK-cells. The procedure packs RNA molecules in a lipid envelope, and once they are inside, they interfere with the expression of the gene responsible for inactivating the cells. The nanoparticles target the killer cells inside the patient’s body, are incorporated into them and, by means of a biochemical reaction, enable them to reduce the tumor mass.
The researchers said their innovation is significant because it can be very efficient in applying already established medical approaches based on NK-cells as well as other treatments. Lipid particles nanotechnology used as an RNA vehicle is a field-proven technology, as was demonstrated in the Covid-19 vaccine. But in contrast to the immune system, Barda-Saad uses it in her lab for temporarily “silencing” gene expression aimed at enhancing the immune response in pathological conditions.
“Our research proved the feasibility of using nanoparticles to enhance immune system activity – in this case of NK-cells – against human hematological malignancies. In the future, particles will be created that can be administered orally to patients,” she said.
“This strategy must still be submitted for pre-clinical and clinical safety testing, as is customary for any drug,” Barda-Saad said. “Its use can be extended beyond cancer: Viral infections and other pathological conditions can also be dealt with by NK-cells as well as by other cell types in the immune system, such as T or B lymphocytes, and for other pathologies.”
The idea to develop nanoparticles came from the fact that they eliminate the need to purify and isolate a patient’s cells outside the body, as in the strategies currently used for treating blood cancers such as chimeric antigen receptor (CAR)-NK or CAR-T. When the nanoparticles are given to the patient, they can independently identify the specific target cell while in the body, penetrate it and change its behavior according to their contents.
In this research, the nanoparticles specifically identify the NK-cells, thanks to the antibody attached to their surface. The NK-cells target the nanoparticles, surround them, and the material inside is released inside the cancerous cell, enabling the natural killer cells to perform their task.
Immunotherapy, especially that which is based on NK-cells, is gaining increasing importance in medicine, Barda-Saad said. “At present, the scientific world is focusing on treatment strategies involving NK-cells because it has been proven that in some aspects, they are superior to T cells, another variety of immune system cells. Therefore, therapeutic strategies with NKs are evolving. The nanoparticles we developed can further empower these strategies.”
She has no doubt that this technology is a sign of the future: “The use of nanoparticles in this innovative and groundbreaking domain of next-generation immunotherapeutic drugs enhances the immune response against pathogens that cause illness,” she said. “We saw that this technology was successful in Pfizer’s and Moderna’s Covid-19 vaccines, and I firmly believe that by combining it with the right molecules detected in our laboratory, we will be able to harness it in the fight against cancer.”