Advanced cancers can leave patients with few options when the tumors become increasingly aggressive and resistant to treatment. But a new study from researchers at UC San Diego in La Jolla indicates a bioengineered antibody may offer a solution.
A protein called integrin αvβ3 does not appear in normal tissue but can be plentiful in aggressive lung, pancreatic and prostate tumors. Thus it can result in both treatment resistance and metastasis, the process in which cancer cells travel to other parts of the body.
The potential solution presented by UCSD School of Medicine researchers is an anti-αvβ3 antibody that triggers macrophages, a type of immune cell already found in large quantities in advanced tumors.
“Originally [the study] was supposed to make a new drug to target this protein called integrin αvβ3 that is a driver and also a marker of cancer progression,” said study lead Dr. Hiromi Wettersten, an assistant professor in the Department of Pathology at the School of Medicine and a member of UCSD’s Moores Cancer Center.
“And I think we achieved [it]; we made a new antibody that can target integrin αvβ3 cancer cells.”
The antibody sends macrophages to attack tumors by introducing higher levels of inducible nitric oxide synthase, or iNOS — an enzyme that kills infected or cancerous cells with the immune system. The treatment “basically manipulate[s] microphages to become soldiers to fight cancers,” Wettersten said.
The new paper builds on a 2019 study that showed effectiveness in mice. From there, researchers analyzed tumor samples from human patients. Both models showed “powerful anti-tumor responses” and killed cancer cells more effectively, according to a statement from UCSD Health Sciences.
A previous approach — activating natural killer cells in the immune system — “ultimately failed to significantly improve patient survival in clinical outcomes,” the statement said.
The new findings were published Oct. 13 in Molecular Cancer Therapeutics, with funding from the National Institutes of Health, Alpha Beta Therapeutics, San Diego Digestive Diseases Research Center and California Institute for Regenerative Medicine.
The drug next will be up for clinical trials, though Wettersten said a timeline for that is unclear.
“This brings the drug very, very, very close to being used in patients, so I think it’s very significant,” Wettersten said.
Researchers say the study may be a possible blueprint for improving immunotherapies for other treatment-resistant tumors. ♦