DNAtrix is Advancing an Oncolytic Adenovirus Armed with the T-Cell Co-stimulator OX40 Ligand
DNAtrix’s second immunotherapy product candidate, DNX-2440, is a tumor-selective, conditionally replicative oncolytic adenovirus expressing human OX40 ligand (OX40L, CD252, TNFSF4) and is being developed to treat cancer, including metastatic disease. OX40 is a member of the tumor necrosis factor receptor superfamily, and interactions between OX40 and OX40L act as co-stimulatory signals for T-cell activation.
DNX-2440 works by establishing a robust and specific infection in tumor cells, replicating and triggering both innate and adaptive immune responses. During the viral replication and spreading process within the tumor, functional OX40L is produced and displayed on the tumor cell surface, thereby enhancing memory T-cell survival and suppressing differentiation and activity of regulatory T-cells in the local tumor environment.
Extensive preclinical data show that DNX-2440 triggers an antitumor immune response, tumor-specific immune memory, and an abscopal effect (shrinking of an untreated tumor distant from the treated tumor) leading to prolonged survival in preclinical models of cancer, including gliomas, melanomas, breast, and lung cancers. DNX-2440 recently entered the clinic to treat patients with liver metastasis.