A research team at the University of California, Irvine has developed a new type of immunotherapy that targets a broad range of cancers without damaging healthy tissue. The study, led by Michael Demetriou, MD, PhD, found that these therapies use engineered proteins to bind specifically to complex carbohydrate chains called glycans, which are abundant on cancer cells but rare in normal tissue.
The researchers created two compounds, GlyTR1 and GlyTR2, which act as glycan-dependent T cell recruiters. These compounds were shown to be safe and effective in preclinical models for various cancers such as breast, colon, lung, ovarian, pancreatic, and prostate cancers. The findings were published in the journal Cell.
“It’s the holy grail – one treatment to kill virtually all cancers,” said Demetriou. “GlyTR’s velcro-like sugar-binding technology addresses the two major issues limiting current cancer immunotherapies: distinguishing cancer from normal tissue and cancer’s ability to suppress the immune system.”
Marian Waterman, PhD, former deputy director of research at UCI Health Chao Family Comprehensive Cancer Center commented on the significance of the work: “This landmark study is a paradigm shift with the very real potential to change how we treat cancer patients.” Richard A. Van Etten, MD, PhD, director of the center added: “This novel technology may, for the first time, allow the widespread application of targeted T-cell therapy to solid tumors, which is the ‘holy grail’ in the immuno-oncology field.”
Traditional treatments like CAR T therapy have mainly been effective against blood cancers such as leukemia. The new GlyTR approach was also effective against leukemia in preclinical studies.
Instead of focusing on protein biomarkers unique to certain cancers—a common strategy—Demetriou’s team targeted glycans because they form a dense coating on tumor cells while being scarce on healthy cells. Although glycans are common cancer antigens, they have not been widely used for targeting due to their inertness to immune responses. The GlyTR compounds overcome this limitation by binding selectively to glycan-rich tumor cells and marking them for destruction by immune cells.
The next step involves testing GlyTR’s safety and effectiveness in human patients. Clinical-grade manufacturing is underway at NCI Experimental Therapeutics program labs in Maryland. Phase 1 clinical trials could begin within about two years and will focus on patients with metastatic solid tumors who typically have high glycan density and limited treatment options.
“This is the revolutionary approach to cancer treatment our patients have been waiting for,” said Farshid Dayyani, MD, PhD. “We are committing all available resources to bring this exciting new trial to UCI Health as fast as possible.”
Demetriou’s group continues development with additional funding from grants including $2.4 million from an NCI Small Business Technology Transfer Grant and $4.6 million from the California Institute for Regenerative Medicine (CIRM) for further clinical-grade production and trials. Early support came from UC Irvine initiatives such as a pilot project award from its Anti-Cancer Challenge fundraising event.
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