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E3LΔ83N-TK- is an attenuated oncolytic vaccinia virus (Western Reserve strain) engineered for cancer immunotherapy. It features two primary genetic modifications designed to enhance safety and tumor selectivity: a deletion of the N-terminal 83 amino acids of the E3L gene (E3LΔ83N), which removes the Z-DNA-binding domain and results in approximately 1000-fold attenuation of the virus, and a deletion of the thymidine kinase (TK) gene. The TK deletion restricts viral replication to rapidly dividing cells, such as tumor cells, which provide the necessary nucleotides for viral synthesis. Developed by researchers at Memorial Sloan Kettering Cancer Center in collaboration with Sound Biologics, this virus serves as a potent oncolytic backbone for the delivery of immunomodulatory payloads, including FMS-like tyrosine kinase 3 ligand (Flt3L) and immune checkpoint blockade antibodies, to stimulate antitumor immune responses.
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