Oncology, Immunology
Inhibition of PTPN22 to Enhance Antitumor Immunity
2023 Harrington Scholar-Innovator
The fourth leading cause of cancer deaths worldwide, metastatic pancreatic ductal adenocarcinoma (PDA) has few treatment options. Dr. Ho and his team have harnessed the immune system in animal models in a way that raises new hope. They found a viable target for overcoming resistance to immunotherapy that could be leveraged in comprehensive treatment strategies for PDA and potentially, other cancers.
“Our findings show that Protein Tyrosine Phosphatase Non-receptor Type 22 (PTPN22)—a key regulator of T-cell receptor (TCR) signaling that leads to tumor growth in pancreatic and breast cancers—is a druggable target,” Dr. Ho says. “In experiments with mouse models, we observed that when PTPN22 signaling is absent, immune system function is strengthened. Subsequently, we tested a novel small molecule agent, L1, to inhibit PTPN22 and we found the same effect.”
Dr. Ho and his team have developed an assay to better understand PTPN22 expression in other human cancers and are working to further characterize it through their access to Johns Hopkins University’s robust biorepository of cancer specimens. With Harrington assistance, the next translational step they hope to achieve is L1 optimization. Because L1 synergizes with a class of drugs already on the market and in use for chemotherapy, it has strong potential for augmenting anticancer immunity and greatly improving patient outcomes.
“Harrington is a bridge between our increasing knowledge of PTPN22 inhibition and defining the most opportune disease models and medicinal chemistry,” Dr. Ho says. “We are very excited to advance our work with Harrington’s guidance and expertise.”