Department of Neurosurgery, Nara Medical University, Kashihara, Japan
Grandsoul Research Institute for Immunology, Inc., Uda, Japan.
Anticancer Res. 2020 Jun;40(6):3231-3237. doi: 10.21873/anticanres.14304.
BACKGROUND/AIM: We previously established a novel type of epidermal growth factor receptor variant III (EGFRvIII)-specific chimeric antigen receptor (CAR)-expressing natural killer (NK) cell line, designated EvCAR-KHYG-1, which inhibited the growth of glioblastoma (GBM) cells in vitro via apoptosis.
We investigated the cytokine-producing effect of EvCAR-KHYG-1 cells on GBM-like cell lines and their antitumour effect using in vivo xenograft assays.
EvCAR-KHYG-1 cells produced interleukin-2, interferon-γ, and tumour necrosis factor-α on EGFRvIII-expressing U87MG cells. In vivo xenograft assays showed that EvCAR-KHYG-1 cells did not reduce the volume of subcutaneous tumours derived from EGFRvIII-expressing U87MG cells but did reduce tumour cell occupancy.
EvCAR-KHYG-1 cells led to expression of cellular immunity-related cytokines on EGFRvIII-expressing U87MG in vitro but did not inhibit tumour progression due to the induction of a pseudo progression-like pathological feature. Future studies investigating the effect of different conditions in vivo are required to study the inhibition of tumour progression in GBM.
背景/目的:我们之前建立了一种新型的表皮生长因子受体变体 III(EGFRvIII)特异性嵌合抗原受体(CAR)表达的自然杀伤(NK)细胞系,命名为 EvCAR-KHYG-1,它通过细胞凋亡抑制体外胶质母细胞瘤(GBM)细胞的生长。
我们研究了 EvCAR-KHYG-1 细胞对 EGFRvIII 表达的 U87MG 样细胞系的细胞因子产生效应,并通过体内异种移植实验研究了其抗肿瘤效应。
EvCAR-KHYG-1 细胞在表达 EGFRvIII 的 U87MG 细胞上产生白细胞介素-2、干扰素-γ 和肿瘤坏死因子-α。体内异种移植实验表明,EvCAR-KHYG-1 细胞并没有减少源自表达 EGFRvIII 的 U87MG 细胞的皮下肿瘤体积,但确实减少了肿瘤细胞的占有率。
EvCAR-KHYG-1 细胞在体外诱导 EGFRvIII 表达的 U87MG 细胞表达细胞免疫相关细胞因子,但由于诱导出一种假进展样的病理特征,并未抑制肿瘤进展。未来需要研究不同条件下体内的效应,以研究对 GBM 中肿瘤进展的抑制作用。