This is the first study to establish a CAR NK cell line based on the human NK cell line KHYG-1. Therapy with EvCAR-KHYG-1 may be an effective treatment option for GBM patients.

Glioblastoma is the leading malignant glioma with a poor prognosis. This study aimed to investigate the antitumor effects of natural killer cells in combination with temozolomide as the standard chemotherapeutic agent for glioblastoma. Using a simple, feeder-less, and chemically defined culture method, we expanded human peripheral blood mononuclear cells and assessed the receptor expression, natural killer cell activity, and regulatory T cell frequency in expanded cells. Next, using the standard human glioblastoma cell lines (temozolomide-sensitive U87MG, temozolomide-resistant T98G, and LN-18), we assessed the ligand expressions of receptors on natural killer cells. Furthermore, the antitumor effects of the combination of the expanded natural killer cells and temozolomide were assessed using growth inhibition assays, apoptosis detection assays, and senescence-associated β-galactosidase activity assays in the glioblastoma cell lines. Novel culture systems were sufficient to attain highly purified (>98%), expanded (>440-fold) CD3 − /CD56 + peripheral blood-derived natural killer cells. We designated the expanded population as genuine induced natural killer cells. Genuine induced natural killer cells exhibited a high natural killer activity and low regulatory T cell frequency compared with lymphokine-activated killer cells. Growth inhibition assays revealed that genuine induced natural killer cells inhibited the glioblastoma cell line growth but enhanced temozolomide-induced inhibition effects in U87MG. Apoptosis detection assays revealed that genuine induced natural killer cells induced apoptosis in the glioblastoma cell lines. Furthermore, senescence-associated β-galactosidase activity assays revealed that temozolomide induced senescence in U87MG. Genuine induced natural killer cells induce apoptosis in temozolomide-sensitive and temozolomide-resistant glioblastoma cells and enhances temozolomide-induced antitumor effects in different mechanisms. Hence, the combination of genuine induced natural killer cells and temozolomide may prove to be a promising immunochemotherapeutic approach in patients with glioblastoma if the antitumor effects in vivo can be demonstrated.

This is a case report of an unusual aneurysm of the distal anterior inferior cerebellar artery. A 44-year-old woman had a severe frontal headache and vomiting of sudden onset. On the day after admission, the patient began to demonstrate nuchal rigidity and difficulty with upward gaze bilaterally. There were no complaints at this time suggestive of a syndrome of the cerebellopontine angle. A computed tomographic scan revealed an intraventricular hemorrhage of the 3rd and 4th ventricles; however, multiple attempts at four-vessel angiography were required before an aneurysm could be demon-strated. On the 28th hospital day, a suboccipital craniectomy using the retromastoid approach in the lateral position was performed. A saccular aneurysm with a surrounding hematoma in the distal anterior inferior cerebellar artery was found and clipped. The operative findings revealed that the aneurysm was unrelated to the cerebellopontine angle. After surgery, the patient had an uneventful recovery and complete resolution of symptoms.