UCI researchers receive $3.4 million grant to study new class of cancer killing immunotherapeutics

UCI School of Medicine researchers have been awarded a $3.4 million grant by the National Cancer Institute (NCI) as part of the Beau Biden Cancer Moonshot initiative. The funding will support efforts to provide proof of principal data for an entirely new class of cancer killing immunotherapeutics with the potential to treat highly diverse types of cancer, from leukemia to breast cancer.

Principal investigator, Michael Demetriou, MD, PhD, a professor of neurology, microbiology and molecular genetics and member of the NCI-designated Chao Comprehensive Cancer Center at UCI, will lead the study entitled, "N-glycosylation and immunotherapy for cancer."

"This grant epitomizes the kind of bench-to-bedside translational cancer research that is emerging from our NCI-designated cancer center," said Richard Van Etten, MD, PhD, director of the UCI Chao Family Comprehensive Cancer Center. "Dr. Demetriou's work, supported in part by a seed grant from the UCI Anti-Cancer Challenge event, has the potential to change our current paradigm of cancer immunotherapy by defining a class of new cancer-specific antigens that are broadly applicable to many tumors. We look forward to shepherding this class of therapeutic agents towards a clinical trial in patients."

For decades, the treatment of cancer has relied on surgical resection, chemotherapy and/or radiotherapy, and new immune-based therapies offer promising new options for cancer treatment. The most potent of these--bi-specific antibodies that cross-link T cells to cancer cells and T cells engineered to express antigen receptors specific to cancer cells (CAR T cells)--induce T cell mediated killing of cancer cells and display extraordinary complete response rates up to ~90% for B cell cancers. However, broadly applying these types of cancer treatments is greatly limited by a lack of protein antigens that can be safely targeted without toxicity. In addition, different versions of these treatments need to be made for each different cancer type, greatly increasing time and cost of development.

Demetriou and his post-doctoral fellow, Raymond Zhou, PhD, have worked to overcome these barriers by inventing a novel technology called Glycan dependent T cell Recruiter (GlyTR - pronounced 'glitter') using pilot funding from the UCI Center for Applied Innovation, the UCI Institute for Clinical and Translational Science and the UCI Anti-Cancer Challenge Research Fund.

Almost all proteins on the surface of cells have complex sugars attached to them. Abnormal expression of these complex sugars, or 'glycans', is nearly a universal feature of cancer and provides the most abundant and widely expressed cell surface cancer antigens known while also having limited or no expression in normal tissue. The generation of potent antibodies specific to these abnormal cancer glycans has proven to be challenging, greatly limiting their usefulness as targets for cancer immunotherapy.

"GlyTR is a disruptive immunotherapy platform technology that can markedly broaden the types of cancers sensitive to immunotherapy by effectively targeting abnormal glycans," said Demetriou. "We are very excited that the Biden Cancer Moonshot program and the NCI have recognized the great potential of GlyTR technology in the fight against cancer."

Now funded through the Moonshot Initiative, the UCI team will proceed with characterizing GlyTR technology targeting N-glycans, and examine the efficacy and safety using mouse models. To translate the GlyTR technology to humans, Demetriou and Zhou co-founded a company called GlyTR Therapeutics in 2016 to accelerate the application of GlyTR immunotherapy to treat cancer in humans. The company is supported by UCI Applied Innovation and is incubating at EvoNexus in Irvine, CA.

As a grant recipient, the UCI research team becomes part of the NCI's Immuno-Oncology Translation Network, which was established to foster collaborative team science approaches to accelerate the discovery of new immune targets and evaluate novel immune-based therapies and combination approaches that eliminate established cancers in adults or to prevent cancers before they occur. As members of the Immuno-Oncology Translation Network (IOTN), the UCI research team will meet regularly with the other awardees to advance immunotherapies for cancer.

The Cancer Moonshot initiative was established to accelerate cancer research and aims to make more therapies available to more patients, while also improving our ability to prevent cancer and detect it at an early stage.