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腹腔注射 NK-92 改善早期与已成瘤卵巢癌模型异种移植瘤的生存

英文原题:Intraperitoneal administration of NK-92 improves survival in xenografts of early and established ovarian cancer models.

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Intraperitoneal administration of NK-92 improves survival in xenografts of early and established ovarian cancer models.

PubMed 2026/04/20(内容时间) PLoS One Q2 · IF 2.8(JCR 2025)

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中文摘要

卵巢癌(OC)是妇科癌症相关死亡的主要原因。由于该疾病在诊断时通常已出现腹腔内转移,标准治疗可能伴随严重并发症,且疾病复发常见,因此管理仍然具有挑战性。虽然细胞免疫治疗作为有前景的方法正日益受到研究,但最有效的给药途径仍需确定。

我们研究了NK细胞治疗作为一种毒性较低的选项,并考察了永久性NK细胞系NK-92作为合适模型。在此,我们报告了两种使用卵巢腺癌细胞系SKOV-3的异种移植小鼠模型,分别代表早期OC和伴有腹水的晚期OC,以全面评估不同NK-92给药途径的抗癌疗效。采用生物发光成像、IVIS系统细胞追踪和动物生存来评估结果。细胞通过腹腔内(IP)、静脉内(IV)或IP与IV联合途径给药。

我们发现,在早期和已建立的OC异种移植中,NK-92通过IP给药(p = 0.009和p = 0.018)或IP与IV联合给药(p = 0.05和p = 0.017)显著提高了动物生存,而相似剂量的静脉给药与未治疗对照相比对生存无影响(p = 0.665和p = 0.052)。这些发现及我们的新模型,对于增强NK治疗在晚期OC患者中的临床获益具有潜在意义。

展开英文摘要原文

Ovarian cancer (OC) is a leading cause of gynecological cancer-related mortality. Management remains challenging as the disease frequently presents with intra-abdominal metastases at diagnosis, standard therapies can be associated with severe complications and disease recurrence is common. While cellular immunotherapy is increasingly investigated as a promising approach, the most effective routes of administration need to be established.

We have investigated NK cell therapeutics as a less toxic option and examined the permanent NK cell line, NK-92, as a suitable model.

Here, we report two xenograft mouse models with the ovarian adenocarcinoma cell line, SKOV-3, representing early-stage OC and late-stage OC with ascites to comprehensively evaluate the anti-cancer efficacy of different routes of NK-92 administration. Bioluminescence imaging, cell tracking with the IVIS system and animal survival were used to evaluate outcomes. The cells were administered via intraperitoneal (IP), intravenous (IV), or a combination of IP and IV routes.

We showed that NK-92 significantly increased animal survival when delivered IP (p = 0. 009 and p = 0. 018) or combined IP and IV (p = 0. 05 and p = 0. 017) in early and established OC xenografts, respectively, whereas intravenous delivery at similar doses had no effect on survival (p = 0. 665 and p = 0. 052) compared with untreated controls.

These findings, and our novel models, have potential implications for enhancing the clinical benefit of NK therapy in patients with advanced OC.

论文信息

作者
Marcus P、Warrington J、Zhang M、Ankathatti-Munegowda M、Wang XH、Rashedi I、Keating A
单位
Krembil Research Institute, University Health Network, Toronto, Ontario, Canada.Canada
期刊
PloS one2026
原文标识
PubMed 42008496 · DOI 10.1371/journal.pone.0347095