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How a long-known biomarker backs BioNTech’s antibody for pancreatic cancer

Blocking CA19-9 could serve as a therapeutic strategy to prevent the progression from chronic pancreatitis to pancreatic cancer, scientists at Cold Spring Harbor Laboratory have found. (Tuveson lab/CSHL 2019)

CA19-9, or sialyl-Lewis, is a sugar molecule that’s present on many proteins and is often elevated in patients with pancreatitis and pancreatic cancer. Therefore it has been used for more than 30 years to assess disease burden. But now a team of scientists at Cold Spring Harbor Laboratory (CSHL) have found that CA19-9 may, in fact, promote the development of these pancreatic diseases.

The team found that blocking CA19-9 could serve as a therapeutic strategy to prevent the progression from chronic pancreatitis to pancreatic cancer. The findings were just published in the journal Science, but they have already been translated into an antibody drug acquired by BioNTech called MVT-5873.

The CA19-9 antibody is already in clinical testing for pancreatic cancer and has turned up positive interim data from a phase 1. The drug was recently snapped up by German biotech BioNTech from now-bankrupt MabVax Therapeutics. In addition, a pending patent application filed by CSHL covering the use of CA19-9 antibodies for pancreatitis has also been exclusively licensed to BioNTech.

“The Science paper is a significant contribution to evaluating MVT-5873 and further validates sialyl Lewis A …as an interesting therapeutic target in pancreatic cancer and pancreatitis,” BioNTech said in a statement sent to FierceBiotechResearch.

Dannielle Engle and colleagues at CSHL started by building a transgenic mouse model that expresses CA19-9. They were surprised to find that the rodents developed severe pancreatitis. Previous studies had established that EGFR signaling is responsible for the induction of pancreatitis and also tumor formation. Engle’s team also observed that the transgenic mice over-expressed EGFR.

In the animals, CA19-9 recruited the immune system to repair injuries caused by pancreatitis, and by doing so, it triggered a cascade of events that led to accelerated tumor formation, the researchers found.

By using antibodies directed against CA19-9, the team successfully reversed pancreatitis in the mice. What’s more, blocking CA19-9 seemed to be more effective for treating pancreatitis than administering Roche’s Tarceva, which inhibits EGFR.

“Pancreatitis is required for developing pancreatic cancer, and we might be able to prevent that transition in patients with pancreatitis by targeting CA19-9,” Engle said in a statement.

Pancreatic cancer is notoriously hard to treat. One reason is the lack of effective biomarkers to help clinicians detect the disease early. EGFR inhibitors such as Tarceva have shown little benefit in the late stages of the disease.

Due to a lack of effective treatments, scientists are working on a range of different approaches to attack pancreatic cancer. Researchers at the University of North Carolina found that a combination of a MEK inhibitor and hydroxychloroquine, a drug used to treat malaria, could offer a two-pronged attack at pancreatic cancer. A team of scientists led by the University of Pittsburgh discovered that some patients with certain genetic signatures might respond well to existing chemotherapies.

Meanwhile, in a Perspective piece that ran alongside the new CSHL study, two scientists at the University of Michigan argue that the CA19-9 mouse model and organoids derived from them could be used to distinguish pancreatitis from cancerous cells, serving a role in the early detection of pancreatic cancer.