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South Korean scientists recently published data showing that novel, cell-penetrating antibodies targeting the RAS gene family, produce anti-tumor activity in mice.

The RAS gene family is one of the most commonly mutated oncogenes, or a gene that has the potential to cause cancer, and is involved in about 30 percent of all human cancers.

Researchers have been attempting to develop therapies that target RAS for more than 30 years, but have been largely unsuccessful.

“Discovered nearly 35 years ago, the mutant RAS protein has been considered a highly-validated cancer drug target, but also has a reputation as being undruggable,” Yong Sung Kim, Ph.D., principle investigator on the recent paper, co-founder of Orum Therapeutics, and professor in the Department of Molecular Science and Technology at Ajou University in Korea, said in a prepared statement.

Orum Therapeutics is a private biotech company developing a new class of therapeutic antibodies to treat severe genetic diseases and cancer.  The company along with scientists at Ajou University developed a novel monoclonal antibody called RT11-i, which is internalized by the cell and directly targets the activated form of RAS.

Along with playing a part in tumor formation, tumors with activating RAS mutations often don’t respond to current treatment options, such as the EGFR-targeting drug, cetuximab.

The new data, published May 10 in Nature Communications, showed the antibody bind specifically to activated RAS inside the cell and blocked interaction with effector proteins, inhibiting downstream oncogenic signaling.

The drug was shown to inhibit tumor growth in several xenograft models of tumor-bearing mice, and was well tolerated.

“This data shows that with our cell penetrating antibody technology, we now have the ability to selectively inhibit activated RAS to achieve anti-tumor activity with a systemically administered monoclonal antibody,” Kim explained.

Patients with advanced colon cancer who have oncogenic RAS mutations might benefit from a combination of RT11-I and an anti-EGFR treatment, additional data from the study suggests.

Tests on a xenograft mouse model of colorectal cancer resistant to anti-EGFR therapy cetuximab, showed that doses of both the antibody and cetuximab caused the animals to overcome cetuximab resistance. 

“As an anti-cancer therapy, our cell penetrating antibodies are easy to produce, allow for systemic administration that is well tolerated, and have pharmacological properties,” Sung Joo Lee, Ph.D., co-founder and CEO or Orum Therapeutics said in a statement. “We believe this could be a very important first-in-class therapeutic for hard-to-treat pancreatic, colon, and non-small cell lung cancers.”

Contributing Editor/Science Writer
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