Delta-24-RGD-H43m

Delta-24-RGD-H43m is a chimeric oncolytic adenovirus engineered to treat recurrent glioblastoma and other high-grade gliomas. It is a modified version of the parental oncolytic virus Delta-24-RGD (also known as DNX-2401), which is based on adenovirus serotype 5 (Ad5). To circumvent the neutralizing antibodies (NAbs) that frequently develop in patients following initial treatment with Ad5-based vectors, Delta-24-RGD-H43m features a hexon-swap modification. Specifically, the hypervariable regions (HVRs) of the Ad5 hexon protein have been replaced with those from the rare serotype 43 (Ad43). This engineering allows the virus to evade pre-existing or induced anti-Ad5 immunity while maintaining the infectivity, replication, and oncolytic potency of the original virus. The virus retains the 'Delta-24' mutation (a 24-bp deletion in the E1A region) for tumor selectivity via the Rb pathway and the 'RGD' motif in the fiber knob to enhance entry into glioma cells via integrins.