Figure 6. Primary human SCLC specimen is permissive to MYXV, and a direct intratumoral delivery of MYXV to human SCLC PDX tumors shows viral replication and extensive tumor necrosis.

(A) Primary SCLC patient specimen collected from bronchoscopy was immediately infected with vMyx-GFP-TdT at 10 MOI, demonstrating both early (GFP) and late (TdTomato) gene expression for replication at 48 hours. Scale bars, 200 μm. Early infection is evident at 24 hours and replication propagating through the patient specimen is evident by 48 hours. (B) Primary SCLC patient specimen infected with vMyx-M135KO-GFP at 10 MOI shows expression of early/late (GFP) gene expression at 48 hours. Scale bars, 200 μm. vMyx-M135KO-GFP lacks a TdTomato reporter gene and expression of the GFP reporter gene is under a poxvirus synthetic early/late promoter expressing GFP during both infection and replication stages. (C) Patient-derived xenograft (PDX) tumor after direct intratumoral injection (5 × 10⁷ FFU in 50 μl PBS) of vMyx-FLuc expressing Firefly luciferase under poxvirus synthetic early/late promoter indicating viral infection and replication. (D) Histological analysis of H&E stained FFPE sections from PDX tumors at 4 and 7 days after vMyx-FLuc injection (5 × 10⁷ FFU in 50 μl PBS) showing progressively increasing necrosis. vMyx-M135KO-GFP infection illustrates similar necrotic effects as vMyx-FLuc at 7 days. Scale bars, 500 μm. Percentage of tissue area showing necrosis is indicated in each micrograph.