oHSV-BP2mt

oHSV-BP2mt is a next-generation oncolytic herpes simplex virus-1 (oHSV) engineered to treat glioblastoma (GBM) by addressing both intrinsic and extrinsic resistance mechanisms. The virus is designed to secrete a protease-resistant form of Insulin-like growth factor binding-protein 2 (IGFBP2) that contains a mutated RGD domain. This modification allows the drug to target IGF-dependent resistance by sequestering Insulin-like growth factors (IGF1 and IGF2) with high affinity, thereby preventing the activation of the IGF1 receptor (IGF1R). Simultaneously, the RGD mutation prevents the IGF-independent pro-tumorigenic functions of IGFBP2, such as binding to α5β1-integrin. Preclinical studies indicate that oHSV-BP2mt enhances viral replication and spread, particularly in oHSV-resistant cells, and significantly improves survival in orthotopic GBM models compared to standard oHSV therapy.