Efficient ADCC killing of meningioma by avelumab and a high-affinity natural killer cell line, haNK

JCI Insight. 2019 Oct 17;4(20):e130688. doi: 10.1172/jci.insight.130688.


Meningiomas are the most common adult primary tumor of the central nervous system, but there are no known effective medical therapies for recurrent meningioma, particularly for World Health Organization grade II and III tumors. Meningiomas arise from the meninges, located outside the blood-brain barrier, and therefore may be directly targeted by antibody-mediated immunotherapy. We found that programmed cell death ligand 1 (PD-L1) was highly expressed in multiple human malignant meningioma cell lines and patient tumor samples. PD-L1 was targeted with the anti-PD-L1 antibody avelumab and directed natural killer cells to mediate antibody-dependent cellular cytotoxicity (ADCC) of PD-L1-expressing meningioma tumors both in vitro and in vivo. ADCC of meningioma cells was significantly increased in target cells that upregulated PD-L1 expression and, conversely, abrogated in tumor cells that were depleted of PD-L1. Additionally, the high-affinity natural killer cell line, haNK, outperformed healthy donor NK cells in meningioma ADCC. Together, these data support a clinical trial designed to target PD-L1 with avelumab and haNK cells, potentially offering a novel immunotherapeutic approach for patients with malignant meningioma.

Keywords: Brain cancer; Cancer immunotherapy; NK cells; Oncology; Therapeutics.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antibody-Dependent Cell Cytotoxicity / drug effects*
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / immunology
  • Cell Line, Tumor
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Immunotherapy / methods*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / transplantation*
  • Meningeal Neoplasms / immunology
  • Meningeal Neoplasms / therapy*
  • Meningioma / immunology
  • Meningioma / therapy*
  • Mice
  • Treatment Outcome
  • Xenograft Model Antitumor Assays


  • Antibodies, Monoclonal, Humanized
  • B7-H1 Antigen
  • CD274 protein, human
  • avelumab

Grants and funding

Supported by internal funding, National Cancer Institute,NIH