Tumor control via targeting PD-L1 with chimeric antigen receptor modified NK cells

Failed T cell-based immunotherapies in the presence of genomic alterations
in antigen presentations pathways may be overcome by NK cell-based
immunotherapy. This approach may still be limited by the presence of
immunosuppressive myeloid populations. Here we demonstrate that NK cells
(haNKs) engineered to express a PD-L1 chimeric antigen receptor (CAR)
haNKs killed a panel of human and murine head and neck cancer cells at low
effector-to-target ratios in a PD-L1-dependent fashion. Treatment of
syngeneic tumors resulted in CD8 and PD-L1-dependent tumor rejection or
growth inhibition and a reduction in myeloid cells endogenously expressing
high levels of PD-L1. Treatment of xenograft tumors resulted in PD-L1
dependent tumor growth inhibition. PD-L1 CAR haNKs reduced levels of
macrophages and other myeloid cells endogenously expressing high PD-L1 in
peripheral blood from patients with head and neck cancer. The clinical
study of PD-L1 CAR haNKs is warranted.