DL922-947

DL922-947 is an oncolytic adenovirus specifically engineered for the treatment of malignancies characterized by a dysfunctional retinoblastoma (Rb) pathway, such as malignant mesothelioma. The virus contains a 24-base pair deletion in the E1A-conserved region 2 (CR2), which is the domain responsible for binding and inactivating the host cell's Rb protein. In normal quiescent cells, this deletion prevents the virus from inducing the S-phase required for viral replication. However, in cancer cells where the G1-S checkpoint is already compromised—a defect present in over 90% of human cancers—the virus can replicate selectively, leading to direct oncolysis and the stimulation of an antitumoral immune response. Preclinical studies have demonstrated that DL922-947 is effective as a single agent and shows synergistic activity when combined with conventional chemotherapy like cisplatin or targeted inhibitors such as the WEE1 kinase inhibitor MK-1775.