Lymphocytic Choriomeningitis Virus Bearing GPC Mutations for Enhanced Tumor Tropism and Strong Anti-Tumor Activity

The development of effective viroimmunotherapies for cancer relies on the ability of replicating viruses to infect the entire tumor tissue and induce comprehensive inflammation within the tumor microenvironment (TME). In this study, we investigate the impact of mutations in the glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV) on tumor cell infectivity, replication, and the immune response. Specifically, we focus on two key positions in GP1 (181 and 185) that significantly enhance tumor cell infectivity and improve CD8+ T cell function in the GP-mutated LCMV strain LCMV P52. Our findings demonstrate that LCMV strain LCMV P52 replicates preferentially in vivo in tumors, exhibits improved tumor penetration, attracts functional CD8+ T cells more effectively to the tumor, and reprograms the tumor toward a more immunogenic microenvironment to allow for effective checkpoint inhibitor combination.