Meningiomas are common primary tumors in the central nervous system (CNS), and surgical resection is the recommended therapy. However, there is no effective treatment for recurrent meningioma. Avelumab targets PD-L1 and affects natural killer cell-mediated antibody-dependent cytotoxic (ADCC) effects in meningiomas in vitro and in vivo. This article provides a new immunotherapy direction for recurrent meningiomas by introducing clinical trials of avelumab and haNK cells targeting PD-L1.
Meningioma
Meningiomas are the most common intracranial tumors in adults. It is more common in women, with M/F ratios of 2/1 or 3/1. Malignant meningiomas are less common. Meningiomas are classified as CNS WHO grade 1-3 according to histopathological features as well as genetic characteristics. The reference treatment for meningiomas is the surgical removal of symptomatic tumors. However, when multiple surgeries and radiation therapy fail to control tumor growth, there is no standard treatment. As a result, high-grade meningiomas that recur multiple times or those meningiomas that cannot be treated surgically, such as aggressive skull base meningioma, remain an existential problem.
Fig.1 Targets and drugs for meningioma.1
Avelumab
Avelumab is a fully human monoclonal antibody drug used to treat Merkel cell carcinoma, renal cell carcinoma, and urothelial carcinoma. It targets protein programmed death ligand 1 (PD-L1).
In January 2017, it was approved for the treatment of gastric cancer.
In March 2017, it was approved for the treatment of Merkel cell carcinoma.
In September 2017, it was approved for the treatment of aggressive skin cancer.
For more Avelumab products, please search on our website!
Method
The activated NK line is designed to express a high-affinity (ha) Fc receptor, enhance ADCC activity, and generate a haNK cell line. In addition, haNK cells are designed to express IL-2 and granzyme B. This study examined PD-L1 levels and ADCC levels in malignant cell lines and low-grade meningiomas. The ability of engineered aNK cell lines haNK and healthy donor NK cells to lyse meningioma cells when cultured with Avelumab was also examined.
Results
Fig.2 PD-L1 is highly expressed in malignant meningioma.2
Fig.3 ADCC of meningiomas is mediated by high-affinity Fc receptors. 2
Fig.4 PD-L1 is regulated by IFN-γ and hypoxia, and can enhance meningioma lysis of haNK cells.2
Fig.5 Avelumab treatment prolonged survival in meningioma mice.2
Fig.6 PD-L1 is necessary for Avelumab-directed meningiomas ADCC.2
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References
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Mair, M.J.; et al. Emerging systemic treatment options in meningioma. Journal of neuro-oncology. 2023, 161(2): 245-258.
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Giles, A.J.; et al. Efficient ADCC killing of meningioma by Avelumab and a high-affinity natural killer cell line, haNK. JCI insight. 2019, 4,(20): e130688.
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