Nano-drug that attacks cancer twice: both improves the effectiveness of chemotherapy and strengthens the immune system
Chemo-immunotherapy, which combines chemotherapy and immunotherapy, is today considered the most advanced standard in the treatment of a variety of cancers. While chemotherapy is used to destroy cancer cells, immunotherapy encourages immune system cells to recognize and attack the remaining cells. But many patients do not respond to chemo-immunotherapeutic treatment, which means that the treatment is not sufficiently focused.
Now, researchers from Tel Aviv University have successfully demonstrated that a transport system based on fatty nanoparticles can treat both chemotherapy and immunotherapy with RNA. The study opens a new opening for a focused and customized war on cancer, and its results have been published in the important journal Advanced Materials. The research was led by Prof. Dan Farr, head of the Nanomedicine Laboratory, who also serves as Vice President of Research and Development at Tel Aviv University and pioneers in the development of RNA drugs worldwide, along with Dr. Siok-Biom Young, a postdoctoral fellow from Korea. The study was funded by an EU ERC grant and a research scholarship from the Korean government.
Prof. Peer and his team are the first in the world to prove that a drug delivery system based on fatty nanoparticles can be produced, which will discharge its charge exclusively in the target cells – both in the cancer cells (for chemotherapy) and in the cells of the immune system (for immunotherapy).
Focused and stronger
“This is one particle that knows how to act in two arenas,” explains Prof. Peer. “It also makes the more chemotherapy-resistant cancer cells more sensitive and it also boosts the immune system cells and makes them more sensitive to the cancer cells. With one targeted nanoparticle we actually provide two different treatments – and at two very different target sites. We tested the development in model animals. “Of two types – model animals with metastatic melanoma and model animals with local solid growth – and in both populations we have seen the two effects of our transport system.”
The new development continues a promising discovery, which showed that an enzyme called HO1 is used by cancer cells to resist chemotherapy and disguise itself from the immune system. In the clinical study, silencing HO1 in the tumor is considered an optimal strategy, but so far attempts to silence the enzyme have been accompanied by severe side effects.
“Chemotherapy-resistant tumors are part of our endless battle with cancer,” says Prof. Peer. “We would like to silence the HO1 enzyme that allows the tumor to develop resistance to chemotherapy, while at the same time allowing it to disguise itself from the immune system. But existing methods are like bombing an ant with an F-16 plane. And expose the tumor to chemotherapy – without producing environmental damage to the healthy cells. Then, the same nanoparticle reaches the T cells of the immune system, and reprograms them to identify the cancer cells. And we give them back the sensitivity to ‘see’ the cancer as something unnatural and attack it. “
“This is the first time that one nanoparticle-based drug with RNA is doing two very different, really opposite jobs,” adds Prof. Peer. “This is a preliminary study of course, but as such it has tremendous potential.”
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