An Engineered IL-15 Cytokine Mutein Fused to an Anti-PD-1 Antibody Improves Intratumoral T Cell Function and Anti-tumor Immunity

The anti-PD-1 antibody-IL-15 cytokine fusion approach was developed to optimally activate intra-tumoral CD8+ T cells. We engineered a fusion protein of a single, potency-reduced, IL-15 mutein and an anti-PD-1 antibody (aPD1-IL15m). This immunocytokine is designed to deliver PD-1-mediated avidity-driven IL-2/15 receptor stimulation preferentially to PD-1-positive tumor-infiltrating lymphocytes (TILs) while reducing the natural preference of IL-15 for circulating peripheral NK or T cells. Overall design: 5x10^5 B16-F10 tumor cells were implanted s.c into mice and tumor resected 11 days post s.c. implantation. Following resection mice were treated with five different treatments.