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Using an RNA-based drug delivered to multiple myeloma blood cancer cells by targeted lipid nanoparticles, researchers at Tel Aviv University (TAU) destroyed 90% of the cells under laboratory conditions and 60% of the cells in human tissues.
Biochemistry lab, working with medical nanoparticles – illustrative photo. Image credit: Pixnio, CC0 Public Domain
The researchers developed lipid-based nanoparticles, similar to those used in the COVID-19 vaccine, containing RNA molecules that silence the gene CKAP5, encoding cytoskeleton-associated protein 5. With this protein inhibited, the cancer cell is unable to divide, which essentially kills it.
To avoid damaging noncancerous cells, the nanoparticles were coated with antibodies that guided them specifically to the cancer cells inside the bone marrow.
The breakthrough was achieved by a group of researchers from TAU and the Rabin Medical Center led by Professor Dan Peer, a pioneer in the development of RNA therapeutics and Head of the Nanomedicine Laboratory at TAU’s Shmunis School of Biomedicine and Cancer Research, and by PhD student Dana Tarab-Ravski.
The results were published on July 27, 2023, in Advanced Science.
“Multiple myeloma is a blood cancer usually found in the older population,” Tarab-Ravski explains. “While most blood cancers appear in the blood stream or lymph nodes and spread from there to the rest of the body, multiple myeloma cells appear and form tumors inside the bone marrow and are therefore very hard to reach.”
The study’s findings are very encouraging. Under laboratory conditions, where cells are grown in flasks, the nanoparticles developed by the researchers eradicated about 90% of the cancer cells.
At the second stage, the new treatment was tested on cancer samples taken from multiple myeloma patients at the haemato-oncological ward of the Rabin Medical Center. The success rate in these samples was 60%.
Testing the ability of the nanoparticles to reach the bone marrow in an animal model, the researchers found that after a single injection the RNA had penetrated to 60% of the multiple myeloma cancer cells in the bone marrow.
Lastly, examining the therapeutic effectiveness of the nanoparticles in the animal model resulted in eradication of two-thirds of the cancer cells, and the animals showed significant improvement in all clinical indicators.
“People with multiple myeloma suffer from severe pain in their bones, as well as anemia, kidney failure, and a weakened immune system,” says Tarab-Ravski.
“There are many possible treatments for this disease, but after a certain period of improvement most patients develop resistance to the therapy and the disease relapses even more aggressively. Therefore, there is a constant need for developing new treatments for multiple myeloma.
“RNA-based therapy has a great advantage in this case because it can be developed very quickly. By simply changing the RNA molecule a different gene can be silenced each time, thereby tailoring the treatment to the progression of the disease and to the individual patient. The drug delivery system we developed is the first that specifically targets cancer cells inside the bone marrow, and the first to show that silencing the expression of CKAP5 gene can be used to kill blood cancer cells.”
Professor Peer, who also serves as TAU’s Vice President of Research and Development, says, “Our technology opens a new world for selective delivery of RNA medications and vaccines for cancer tumors and diseases originating in the bone marrow.”
The clinical team included Dr. Tamar Berger, Dr. Iuliana Vaxman, and Professor Pia Raanani from the Institute of Hematology, Rabin Medical Center. The research was funded by the Varda and Boaz Dotan Research Center in Hemato-Oncology at TAU and by the Lewis Trust for Blood Cancer Research.
Source: AFTAU
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