Combining PDL-1 blockade with agonistic antibodies against 4-1BB enhances T cell restoration after chronic LCMV infection (90.22)

Abstract

The PDL-1:PD-1 pathway is involved in T cell exhaustion after chronic viral infection. PD-1 can bind to either PDL-1 or PDL-2, whereas PDL-1 can bind to either PD-1 or B7.1. We tested the effect of combining standard aPDL-1 blockade with a4-1BB (3H3 agonistic antibody) treatment to determine T cell restoration effects in a model of chronic infection with lymphocytic choriomeningitis virus (LCMV). We chose 4-1BB because it has been shown to be an important costimulatory pathway. It appears that a4-1BB treatment enhances the effect of aPDL-1 blockade if given in a low dose (50 μg, once). Conversely, if a4-1BB is given in a high dose (200 μg, five times), it results in sudden increase of antigen-specific T cells by day 7, but massive T cell death by day 14 post treatment. These results show the importance for 4-1BB costimulation in aPDL-1 mediated T cell restoration.