Tumor control via targeting PD-L1 with chimeric antigen receptor modified NK cells
Yvette Robbins,
Sarah Greene,
Jay Friedman,
Paul E Clavijo,
Carter Van Waes,
Kellsye P Fabian,
Michelle R Padget,
Houssein Abdul Sater,
John H Lee,
Patrick Soon-Shiong,
James Gulley,
Jeffrey Schlom,
James W Hodge,
Clint T Allen
Affiliations
Yvette Robbins
Translational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, United States
Sarah Greene
Translational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, United States
Jay Friedman
Translational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, United States
Paul E Clavijo
Translational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, United States
Carter Van Waes
Tumor Biology Section, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, United States
Kellsye P Fabian
Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, United States
Michelle R Padget
Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, United States
Houssein Abdul Sater
Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, United States
Translational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, United States; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, United States
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.
