CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
Novaferon 基因修饰促进 NK92 细胞抗肿瘤活性
英文原题：Novaferon gene modification promotes NK92 cell anti-tumor activity.
查看英文原题
Novaferon gene modification promotes NK92 cell anti-tumor activity.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
中文摘要
随着CAR-T 细胞疗法的显著发展，过继性免疫疗法为恶性肿瘤的治疗开辟了新的水平。自然杀伤（NK）细胞是这一策略中有前景的替代免疫效应细胞。多种抗肿瘤治疗在很大程度上依赖于I型干扰素（IFN）信号传导。I型IFN增强NK细胞的细胞毒性。Novaferon（nova）是一种通过IFN基因改组产生的新型非天然IFN样蛋白，具有强生物活性。为增强NK细胞的抗肿瘤活性，我们构建了稳定表达nova的NK92-nova细胞。
我们发现，与NK92-vec细胞相比，NK92-nova细胞介导了增强的泛癌抗肿瘤活性。抗肿瘤活性的增强与细胞因子分泌增加相关，如IFN-、穿孔素和颗粒酶B。
同时，NK92-nova细胞中大多数活化受体上调。与NK92-nova细胞共培养后，HepG2细胞上NKG2D配体的表达增加，导致HepG2细胞对NK92细胞介导的细胞溶解敏感性增强。NK92-nova细胞在异种移植模型中显著抑制HepG2肿瘤生长，且无全身毒性。
因此，NK92-nova细胞是一种新颖且安全的癌症免疫治疗策略。
展开英文摘要原文
With significant developments in chimeric antigen receptor T-cell therapy, adoptive immunotherapy has unlocked new levels of treatment for malignancies. Natural killer (NK) cells are promising alternative immune effector cells for this strategy. Multiple anti-tumor therapies are largely dependent on type I interferon (IFN) signaling.
Type I IFNs enhance NK cell cytotoxicity. Novaferon (nova) is an unnatural, novel IFN-like protein produced by gene shuffling of IFN- with strong biological activity. To augment the antitumor activity of NK cells, we generated NK92-nova cells that stably express nova.
We found that NK92-nova cells mediated enhanced pan-cancer antitumor activity compared to NK92-vec cells. The increased antitumor activity was associated with the enhanced secretion of cytokines, such as IFN- , perforin, and granzyme B. Meanwhile, most of the activating receptors were upregulated in the NK92-nova cells.
After co-culture with NK92-nova cells, the expression of NKG2D ligands on the HepG2 cells increased, resulting in an enhanced susceptibility of HepG2 cells to NK92 cell-mediated cytolysis. NK92-nova cells significantly inhibited HepG2 tumor growth in a xenograft model without systemic toxicity.
Therefore, NK92-nova cells are a novel and safe strategy for cancer immunotherapy.
论文信息
- 作者
- Zhang W、Yu B、Meng Q、Pu L、Liu B、Li F
- 第一作者单位
- Department of Pathogenobiology, The Key Laboratory of Zoonosis, Chinese Ministry of Education, College of Basic Medicine, Jilin University, Changchun 130021, Jilin, PR China.China
- 通讯作者单位
- Department of Pathogenobiology, The Key Laboratory of Zoonosis, Chinese Ministry of Education, College of Basic Medicine, Jilin University, Changchun 130021, Jilin, PR China; The Key Laboratory for Bionics Engineering, Ministry of Education, Jilin University, Changchun 130021, Jilin, PR China; Engineering Research Center for Medical Biomaterials of Jilin Province, Jilin University, Changchun 130021, Jilin, PR China; Key Laboratory for Health Biomedical Materials of Jilin Province, Jilin University, Changchun 130021, Jilin, PR China; State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi 830000, Xinjiang, PR China. Electronic address: lifan1956@163.com.China
- 期刊
- International immunopharmacology2023 Sep
- 原文标识
- PubMed 37421776 · DOI 10.1016/j.intimp.2023.110613