Enhanced Efficacy and Safety of ADG153: A Novel Anti-CD47 Monoclonal Antibody Prodrug for Cancer Therapy

The CD47 protein, commonly found on cancer cells, binds to the SIRPα receptor on immune cells, preventing them from attacking tumors. Drugs that target this interaction are being tested in clinical trials for various cancers. However, because CD47 is also present on normal cells like red blood cells, current treatments can cause side effects like anemia.

To address this, a new drug called ADG153 was created. This drug is a human-made antibody that is initially hidden by a special covering. This covering prevents the drug from binding to CD47 in healthy tissues. But in the tumor environment, where certain enzymes are more active, the covering is removed, allowing the drug to bind to CD47 on cancer cells.

Tests in the lab showed that both ADG153 and another drug, Hu5F9, could stop the interaction between SIRPα and CD47, bind to CD47 on cancer cells, and stimulate immune cells to eat cancer cells. However, ADG153 with its covering was much less active in these tests, indicating that it was well-hidden.

Importantly, while both drugs showed similar binding to CD47, ADG153 did not cause red blood cells to clump together, unlike Hu5F9. In animal studies, ADG153 was as effective as Hu5F9 at fighting cancer, but it caused less damage to red blood cells, hemoglobin, and other blood components. Additionally, ADG153 stayed in the body longer and had a higher overall effect than Hu5F9.

Overall, ADG153 is a promising new drug that fights cancer effectively while reducing the risk of side effects related to red blood cells and having favorable properties for how long it stays in the body. This makes it a strong candidate for further development and testing in clinical trials.