Researchers succeeded in producing particles to transport new drugs and doubled the lifespan of mice with human lymphoma

The researchers found a way to deliver the RNA-based drug to the cancer cells using nanosubmarines with a control system that activates the drug exclusively in the cancer cells

Researchers succeeded in producing particles to transport new drugs and doubled the lifespan of mice with human lymphoma
Prof. Dan Farr (Photo: Yonatan Blum)
After isolating a gene to intervene in Mantle Cell Lymphoma in 2012, researchers at Tel Aviv University found a way to deliver the RNA-based drug to the cancer cells, extending the lives of mice injected with cancer cells from patients in Israel.

The new study was conducted by Prof. Dan Farr, PhD student Shiri Weinstein and PhD student Itai Toker from the Department of Cell Research and Immunology at Tel Aviv University, in collaboration with Prof. Pia Raanani from the Department of Hematology at the Rabin Medical Center and Prof. Arnon Nagler from the Department of Medical Hematology at the Sheba Center. The study was jointly funded by the Dotan Center of Tel Aviv University, the Cancer Society, the Hemsley Foundation, the National Science Foundation and the American NIH. The results of the study were published in the journal Proceedings of the National Academy of Sciences (PNAS).

"Mental cell lymphoma is a very rare disease," explains Prof. Farr. "At any given moment, there are about 12 patients with Mantel Cell lymphoma in Israel. And it is also the most difficult disease in this family of diseases. It is an incurable disease with a life expectancy of up to 5-7 years." By genetic sequencing of the cancer cells, Prof. Parr and his team found a mutation in the cyclin D1 gene, a gene that is responsible for cell division, in approximately 85% of Mantel lymphoma patients. "Already in 2012, we published an article that proves that it is possible to suppress the expression of this gene, thereby delaying the division of cancer cells, through RNA interference," Prof. Parr says. "So there is a drug, now we need to understand how to use it, how to lead it to the cancer cell."

RNA interference, or RNAi for short, is a genetic phenomenon that silences the expression of specific genes in a cell. In 2006, Andrew Pierre and Craig Mello won the Nobel Prize in Medicine for discovering the RNAi mechanism, a mechanism that holds great therapeutic promise for disease-adapted medicine. The problem facing attempts to develop RNAi-based drugs today is the problem of transporting the RNAi coils to the designated cells.

Nano-submarines with a control system
"If we simply inject the RNAi into the blood, it will not reach the diseased cells," says Prof. Parr. "That's why we created a kind of miniature submarine, which knows how to navigate its way through the body. Our system has three components: the drug itself, i.e. the RNAi with the appropriate sequence to inhibit the expression of the cyclin D1 gene, is wrapped in a fatty nanoparticle, the walls of which have the GPS - a protein against a receptor called CD38. This protein is an antibody that causes the drug to home in on the right cells. And if, heaven forbid, you inject the particles and the drug reaches the wrong cells, we have added an additional element to our nanosubmarine, a control system that activates the drug exclusively in the cancer cells."

To test the new nanosubmarines, Prof. Parr and his team injected cancer cells from patients into mice. After the diseased mice were injected with the drug, the lifespan of the mice increased from an average of 30 days to 55 days. "We almost doubled the lifespan of the mice," says Prof. Parr. "And we could have continued, but we stopped injecting them with the medicine at some point. After the RNAi finishes suppressing the genetic mutation, the cancer cells, especially those that didn't die, can start dividing again. But if we can silence additional relevant genes, we can further extend life span, with a good quality of life. This is routine maintenance work.

Personalized medicine for each patient
"Today we are approaching the direction of personalized medicine, not only for the patient - also for the disease. We are getting close to a situation where we will receive the information from the patients' own cells, and prepare a personalized RNAi store for them. But this game in the gardens has no meaning if we cannot translate it into new treatment methods in the clinic. This is the goal, and the new system we developed is suitable not only for this rare disease, Mantel type lymphoma, but for a variety of blood cancers, such as leukemia, myeloma and lymphoma. We are not in clinical trials, we are not curing cancer tomorrow morning, but there is a new technology here that is very much worth taking further."

Recent studies