This is one of those unique opportunities where prophylactic intervention of pancreatitis may lead to prevention of pancreatic cancer in at-risk patients, Engle said.
In Cancer Center Director David Tuveson's lab at CSHL, Engle investigated the properties of pancreatic cancer. She zeroed in on CA19-9, a complex sugar structure that coats many proteins but had not previously been ascribed with any particular function. A single enzyme controls the final step in production of CA19-9 in humans, but this enzyme is missing in rodents. Engle generated mice that produced CA19-9, and surprisingly noted that the mice developed severe pancreatitis. Engle's findings position CA19-9 as an attractive therapeutic target for pancreatitis.
In mice, CA19-9 recruits the immune system to repair injuries from pancreatitis. Engle found that during this recruitment process, CA19-9 can also induce a cascade of biochemical reactions propelled by the release of deleterious digestive enzymes from the pancreas. This cascade opens a transformational gateway for cancer to develop and Engle also demonstrated that CA19-9 can dramatically accelerate the growth of pancreatic tumors.
Pancreatitis is required for developing pancreatic cancer, and we might be able to prevent that transition in patients with pancreatitis by targeting CA19-9, posited Engle. By targeting CA19-9 with antibodies in animal models, we were able to reduce the severity of pancreatitis and even prevent it from occurring.
A pending patent application filed by CSHL covering use of CA19-9 antibodies for the treatment and prevention of pancreatitis has been exclusively licensed to BioNTech, a German-based biotech company.