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

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.

• Authors: Amber J Giles, Shuyu Hao, Michelle Padget, Hua Song, Wei Zhang, John Lynes, Victoria Sanchez, Yang Liu, Jinkyu Jung, Xiaoyu Cao, Rika Fujii, Randy Jensen, David Gillespie, Jeffrey Schlom, Mark R Gilbert, Edjah K Nduom, Chunzhang Yang, John H Lee, Patrick Soon-Shiong, James W Hodge, Deric M Park
• Journal: JCI insight (JCI Insight) Vol. 4 Issue 20 (10 17 2019) ISSN: 2379-3708 [Electronic] United States
• PMID: 31536478 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

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

Topics

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