The study findings point to talabostat’s ability to stimulate key cytokines known to play an important role in immunostimulation – the enhancement of the body’s natural defenses against cancer.
Talabostat is believed to work through a novel dual mechanism of action that inhibits select dipeptidyl peptidases (DPPs). DPPs are enzymes that digest proteins found naturally in the body, some of which can regulate tumor growth and immune responses. By inhibiting these select DPPs, talabostat has been shown in preclinical models to cause an increase in IL-1 beta, a cytokine believed to play an important role in the positive regulation of immune responses, which in turn stimulates the production of a variety of cytokines and chemokines that promote the anti-tumor activity of neutrophils, macrophages and T lymphocytes.
Talabostat also inhibits fibroblast activation protein (FAP), a DPP located in the tumor stroma, which is the connective tissue supporting tumor growth.
“These results are interesting because they speak to talabostat’s ability to stimulate key cytokines that are believed to play an active role in talabostat’s anti-tumor activity by upregulating both the innate and acquired immune system,” said Dr Charles Dinarello, a professor of medicine at the University of Colorado School of Medicine. “The very nature of talabostat’s dual mechanism of action through both immunostimulation and FAP inhibition speaks to its potential versatility as a targeted agent with broad utility in several different cancers.”