Goal: Provide a biological rationale for biomarker-guided testing of antibody drug conjugates in FLC
Principal Investigator: Mark Yarchoan, MD
Grant length: Six months
Study overview: Cancer cells often overexpress many proteins on their surface. Because of these differences, cancer cells can have unique surface “signatures” that can be used to specifically target them with therapies. These molecules can also be used as biomarkers.
Antibody–drug conjugates (ADCs) are an important class of targeted therapies. ADCs use antibodies that recognize specific proteins on cancer cells to deliver toxic drugs directly to the tumor, reducing damage to normal cells. This strategy has already shown major success in certain cancers. For example, in breast cancer patients with high levels of the HER2 surface protein, HER2-targeted ADCs have significantly improved outcomes. FDA has approved the HER2 ADC for all solid cancers that overexpress a certain level of HER2 molecule. Interestingly, some FLC patients also overexpress HER2, making them potential candidates for treatment with the FDA-approved ADC, ENHERTU. Currently, more than 100 ADCs are being developed that target different surface proteins common to various cancers.
This grant focuses on identifying cell surface proteins that are expressed in FLC that are being targeted by ADCs under development. The team will analyze patient tumor samples from the Johns Hopkins and the FCF Biobank to profile ADC-relevant surface antigens on the tumor cells. Such a systematic characterization of highly expressed surface molecules in FLC could open new treatment options for patients, potentially by repurposing currently available or soon-to-be-approved ADCs.