Overcoming CD155-Driven Immune Resistance in Cholangiocarcinoma

Dr. Funda Meric-Bernstam, professor and chair of the Department of Investigational Cancer Therapeutics at MD Anderson Cancer Center, is investigating whether CD155-targeted antibody-drug conjugates (ADCs) can provide a new treatment approach for patients with cholangiocarcinoma, a rare and difficult-to-treat disease.

Cholangiocarcinoma is a rare but devastating disease with one of the poorest outcomes in oncology. Most patients are diagnosed when the cancer is already advanced and cannot be surgically removed. Even with the best available treatments, survival is often measured in months, and fewer than one in ten patients live five years beyond diagnosis. One reason treatments fail is that cholangiocarcinoma tumors suppress the body’s immune response, making it harder for immune cells to recognize and destroy cancer. One key driver of this immune resistance is CD155, a tumor-associated protein that promotes cancer progression while blocking immune cell activation. This project evaluates whether antibodies that specifically recognize CD155 can safely deliver potent cancer-killing drugs directly into tumor cells while limiting damage to healthy tissue. What makes this approach unique is its potential to combine direct tumor killing with removal of an immune “shield” that allows cholangiocarcinomas to evade immune attack. The long-term goal is to develop a more effective treatment that improves outcomes for patients with cholangiocarcinoma.