Israeli scientists use mRNA COVID-19 vaccine technology to fight cancer

Life expectancy increased by 30% to 80% in mice models

By MAAYAN JAFFE-HOFFMAN
Updated: NOVEMBER 25, 2020 06:30
CRISPR research illustration. (photo credit: ELLA MARU STUDIO)
CRISPR research illustration.
(photo credit: ELLA MARU STUDIO)
For more than a decade, scientists have dreamed about the seemingly endless possibilities of messenger RNA (mRNA).
Now, the world is likely to have two anti-coronavirus vaccines based on mRNA technology to help slow the aggressive pandemic that has killed 1.4 million people.
In Israel, researchers at Tel Aviv University are using a similar technology as Pfizer and Moderna to target cancer cells and genetically neutralize them, increasing overall survival rate.
“When we first spoke of treatments with mRNA 12 years ago, people thought it was science fiction,” said Prof. Dan Peer, vice president for R&D and head of the Laboratory of Precision NanoMedicine at the Shmunis School of Biomedicine and Cancer Research at Tel Aviv University.
Specifically, the researchers developed what is known as “CRISPR-LNPs,” a lipid nanoparticle-based delivery system that targets cancer cells and destroys them through genetic manipulation. The system carries a genetic mRNA that encodes for the CRISPR enzyme Cas9 that “acts as molecular scissors that cut the cells’ DNA,” a release explained.
CRISPR technology allows researchers to alter DNA sequences and modify gene function.
“Cancer genes are responsible for the proliferation of cancer cells,” Peer said. “We want to cut those genes, so that they will not be active anymore and they will destroy the cancer cells forever.”
But he said that the challenge has been to deliver those “scissors” into the right cells without touching healthy cells – “you don’t want to edit the genome of a healthy cell and kill it.”
So, the researchers placed the mRNA inside a fatty envelope known as a lipid, and injected it either systemically or locally into the tumor. A GPS-like system identifies the cancer cells, unlocks them and destroys them.

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In this most recent experiment, the research team targeted two types of cancer: glioblastoma, the most aggressive type of brain cancer, with a life expectancy of 15 months since diagnosis and a five-year survival rate of only 3%; and metastatic ovarian cancer, a major cause of death among women and the most lethal cancer of the female reproductive system.
The researchers demonstrated that a single treatment with CRISPR-LNPs doubled the average life expectancy of mice with glioblastoma tumors, improving their overall survival rate by about 30%. At the same time, it increased overall survival rate by 80% in a metastatic ovarian cancer mice model.
“This is the first study in the world to prove that the CRISPR genome editing system can be used to treat cancer in a living animal effectively,” Peer said.
“It must be emphasized that this is not chemotherapy. There are no side effects, and a cancer cell treated in this way will never become active again. The molecular scissors of Cas9 cut the cancer cell’s DNA, thereby neutralizing it and permanently preventing replication.”
The findings were published in November 2020 in the peer-reviewed journal Science Advances.
He added that the CRISPR genome editing technology has “revolutionized our ability to disrupt, repair or even replace genes in a personalized manner.”
As noted, the Pfizer and Moderna vaccines are similar. They take nanoparticles – “small beads filled with mRNA” – and inject them in the body, Prof. Cyrille Cohen, head of the immunotherapy laboratory at Bar-Ilan University, explained. Cells eat those particles and “learn” how to make a viral protein. Once they make the protein, the body sees it as a foreign antigen and creates antibodies against it.
“The body’s antibodies and T-cells patrol around until they meet the real virus and then they will stop it from attacking our body,” Cohen said.
“There is much in common between virus and cancer from an immunological standpoint,” he added. “One option to help the immune system to fight cancer is to ‘reprogram’ it to recognize cancer associated proteins – targets that can discriminate between healthy and tumor cells. Thus, you could give your body the genetic information coding for these ‘cancer proteins’ to stimulate the immune system to attack the cancer cells.”
Another idea is what Peer is doing in his lab. In fact, Peer said that he developed a lipid delivery system that was sold to BioNTech, the company working with Pfizer to develop its COVID-19 vaccine.
Prof. Dan Peer. (Photo credit: Tel Aviv University)
Prof. Dan Peer. (Photo credit: Tel Aviv University)
Peer said that his cancer research is still in its infancy. However, “by demonstrating its potential in treating two aggressive cancers, the technology opens numerous new possibilities for treating other types of cancer as well as rare genetic diseases and chronic viral diseases such as AIDS.”
He told The Jerusalem Post that the team also intends to experiment with the technology on genetic diseases, such as Duchenne muscular dystrophy, as well.
He said that he hopes to start human trials within the next 18 months to three years.
“I believe that in the near future, we will see many personalized treatments based on genetic messengers – for both cancer and genetic diseases,” Peer said. “I am optimistic.”


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