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

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

Author information

1
Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
2
Neurosurgical Department, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
3
Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
4
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NIH), Bethesda, Maryland, USA.
5
Department of Neurosurgery, University of Utah, Salt Lake City, Utah, USA.
6
NantKwest, Culver City, California, USA.
7
Department of Neurology and the Committee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, Illinois, USA.

Abstract

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

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