oHSV-D11mt

oHSV-D11mt is an engineered oncolytic herpes simplex virus type 1 (oHSV-1) designed to overcome tumor resistance mediated by the IGF2-IGF1R signaling pathway. It incorporates a modified domain 11 of the Insulin-like Growth Factor 2 Receptor (IGF2R) into the viral genome, which acts as a decoy receptor to sequester Insulin-like Growth Factor 2 (IGF2). By neutralizing IGF2, the virus prevents the activation of the IGF1R-MAPK pathway, which is typically upregulated in response to oHSV infection. This modification enhances viral propagation, increases direct tumor cell lysis, and reprograms the tumor microenvironment by reducing the infiltration of immunosuppressive neutrophils and myeloid-derived suppressor cells (MDSCs) while promoting CD8+ T-cell activation. It is being investigated for the treatment of glioblastoma and breast cancer.