HKUST Researchers Develop Glycan-Targeting Therapy to Prevent Breast Cancer Metastasis
HKUST researchers developed LPAT, a glycan-targeting therapy that prevents breast cancer metastasis in mouse models. It completely inhibited metastatic lung tumor onset. Findings published in Biomaterials.
Researchers at the Hong Kong University of Science and Technology (HKUST) have developed a novel glycan-targeting therapeutic strategy called lectin-directed protein aggregation therapy (LPAT) that prevents the onset and growth of metastatic breast cancers in mouse models. The therapy relies on natural proteases secreted by highly metastatic cancer cells to release an activated protein, which self-assembles into a hexameric protein complex that binds strongly to hypersialylated breast cancer cells.
LPAT remains inactive until it encounters proteases in the tumor microenvironment, ensuring activation occurs only at pathological sites. Non-cancerous cells such as red blood cells do not provide the biochemical environment required for activation, resulting in poor binding and mitigation of off-target effects. This design addresses a well-known limitation of monoclonal antibodies, which have been unable to effectively discriminate between cancer-associated glycans and glycans on normal tissues, leading to the clinical failure of many glycan-targeting antibody therapies.
In experiments, the adhesive, invasive, and migratory activities of highly metastatic breast cancer cells were significantly impaired. In vivo studies in murine models demonstrated that the therapy could completely inhibit the onset of metastatic lung tumors in mice. According to the researchers, "The level of glycan discrimination we have observed is not something that can be easily achieved with antibody technology. And since we have only scratched the surface of this technology, we are very excited to further explore the potential for creating a metastasis prevention therapy."
The findings were published in the journal Biomaterials in a study titled "Targeting hypersialylation via lectin-directed protein aggregation therapy (LPAT) for anti-metastasis applications." The modular platform is potentially adaptable to other glycan hallmarks in different cancer subtypes.