NIH grant fuels Liu's work on novel breast cancer treatment

Posted: August 22, 2023

The most common cancer in women worldwide, breast cancer is a genetically and clinically heterogeneous disease with multiple subtypes, including multiple different subtypes possibly existing within a single tumor.

According to the American Cancer Society, the triple-negative breast cancer (TNBC) subtype accounts for about 10-15% of all breast cancers. The term triple-negative breast cancer refers to the fact that the cancer cells don’t have estrogen, progesterone, and human epidermal growth factor receptors. TNBC differs from other types of invasive breast cancer in that it tends to grow and spread faster, has fewer treatment options and tends to have a worse prognosis. New ways to treat TNBC are urgently needed.

Margaret Liu and graduate student research assistant in lab

The National Cancer Institute (NCI) has awarded nearly $2.9 million to Chemical and Biomolecular Engineering Professor X. Margaret Liu, who will lead a team of Ohio State University researchers on a project titled “Dual-payload antibody-drug conjugate for chemo-immunotherapy of triple-negative breast cancers.” The team's goal is to effectively target TNBC by combining their innovative humanized anti-CD276 antibody with a highly potent cancer-killing drug and an immune boosting reagent into one antibody-drug conjugate (276-DualADC).

Liu's group found that in most TNBC patients there is a transmembrane receptor (CD276) which is associated with the growth of new blood vessels that support tumor growth and spreading. In response, the group developed a new monoclonal antibody to target the glycosylated extracellular domain of CD276 and further developed the antibody with high human CD276 specificity and circulation stability.

The scientists then created a dual-payload treatment that functions like a "biological missile," joining the antibody to a cancer-killing drug and immune therapy via novel chemical linkers. The resulting dual-payload antibody-drug conjugate (DualADC) combines the advantages of highly cancer-specific targeting ability with potent killing effect and immunotherapy to achieve accurate and efficient elimination of TNBC cancer cells in vivo. In preliminary evaluations, “276-DualADC” demonstrated highly promising results, effectively targeting CD276 and killing multiple TNBC subtypes while significantly enhancing immune functions and reducing tumor burden by 90-100% in three animal models.

The R01 is the original and historically oldest grant mechanism used by NIH which provides support for health-related research and development based on the mission of the NIH.

Liu earned her PhD from The Ohio State University in 2005.

Read the full article by Wenda Williamson, William G. Lowrie Dept. of Chemical and Biomolecular Engineering

Categories: ResearchFaculty