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

Elife. 2020 Jul 7;9:e54854. doi: 10.7554/eLife.54854.

Abstract

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.

Keywords: NK cells; PD-L1; chimerica antigen receptor; human; immunology; inflammation; mouse; myeloid; syngeneic; xenograft.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • B7-H1 Antigen / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • Humans
  • Killer Cells, Natural / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Receptors, Chimeric Antigen / metabolism
  • Squamous Cell Carcinoma of Head and Neck / metabolism*

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Cd274 protein, mouse
  • Receptors, Chimeric Antigen

Associated data

  • Dryad/10.5061/dryad.sf7m0cg3k