ISRAEL – The Hadassah Cancer Research Institute (HCRI) at the Hadassah University Medical Center in Jerusalem, Israel, is to lead CanceRNA, a global consortium aiming to apply RNA-based therapeutics to successfully unlock anti-cancer immune responses.

Israel Startup Nation is known for its high-tech breakthroughs. But Israel has also been known for its scientific and medical breakthroughs.

Earlier this week, Researchers from Tel Aviv University deciphered, for the first time, a mechanism that enables skin cancer to metastasize to the brain and managed to delay the spread of the disease by 60% to 80% using existing treatments.

And just a few weeks ago, Tel Aviv University researchers also effectively eradicated glioblastoma, a highly lethal type of brain cancer.

The researchers achieved the outcome using a method they developed based on their discovery of two critical mechanisms in the brain that support tumor growth and survival: one protects cancer cells from the immune system, while the other supplies the energy required for rapid tumor growth.

While RNA-based therapies, namely mRNA vaccines, shone during the pandemic and saved millions of lives, they have yet to be successfully tested in cancer therapies.

The HCRI hosted the opening meeting and workshops of CanceRNA in Jerusalem this month to plan, collaborate and advance the aims of the international consortium to impact the future of cancer treatment.

The COVID-19 pandemic has propelled mRNA vaccines into the limelight and researchers are using this as a springboard to design personalized treatments to help train a patient’s own immune system to fight cancer.

The CanceRNA team, led by Michal Lotem, Head of HCRI, the Center for Melanoma and Cancer Immunotherapy, and Rotem Karni, Department Chair at Biochemistry and Molecular Biology, Hebrew University-Hadassah Medical School, will focus on two main goals.

First, will be harnessing the modulation of RNA processing to increase the immunogenicity of “cold” cancers, which lack genomic mutations, to exploit abnormal transcripts and evoke immune response; and second, enhancing the activity of the immune system by retargeting immune effector cells.

A key advance in immunotherapy has been the advent of PD-1 checkpoint inhibitors, monoclonal antibodies that block immune-dampening proteins on T cells.

Some tumors can hijack these receptors to turn off T-cell activity; checkpoint inhibitors release the brakes.

But these drugs don’t work for everyone, and they are less effective against cold tumors that don’t easily attract T cells.

Combining checkpoint blockers with mRNA vaccines could have the effect of letting up on the brakes and stepping on the accelerator at the same time.

Commercialization of mRNA vax technology

CureVac, founded in 2000, was the first company to develop and run clinical studies with mRNA vaccine technology, initially targeting cancer but moving on to other disease areas.

Then, in 2008, BioNTech, based in Mainz, Germany, was founded with the specific aim of developing personalized cancer therapies based on mRNA.

Following this was Moderna, founded in 2010, and several other mRNA start-ups, including eTheRNA in Belgium, which was borne from the work at VUB.

Unlike vaccines for cervical cancer, where a virus underlies the disease, mRNA vaccines are used as a therapy, teaching the body how to fight cancer once it is already present.

There are two main strategies being used to develop mRNA cancer vaccines. First, is a generalized vaccine whereby researchers find proteins that are common to a group of cancers and develop mRNA that can make those proteins, similar to the work at VUB.

Second, a highly personalized vaccine whereby individual tumors are sequenced to develop vaccines based on proteins specific to each person’s cancer, called neo-antigens.

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