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KHYG-1 细胞带有 EGFRvIII 特异性嵌合抗原受体,在源自胶质母细胞瘤样细胞的皮下肿瘤中诱导出一种假性进展样特征。

KHYG-1 Cells With EGFRvIII-specific CAR Induced a Pseudoprogression-like Feature in Subcutaneous Tumours Derived from Glioblastoma-like Cells.

机构信息

Department of Neurosurgery, Nara Medical University, Kashihara, Japan

Grandsoul Research Institute for Immunology, Inc., Uda, Japan.

出版信息

Anticancer Res. 2020 Jun;40(6):3231-3237. doi: 10.21873/anticanres.14304.

Abstract

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.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

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。

材料和方法

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。

结果

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。

结论

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。

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