新型多肽疫苗 GV1001 可保护庆大霉素诱导的耳毒性小鼠模型的听力。

The Novel Peptide Vaccine GV1001 Protects Hearing in a Kanamycin-induced Ototoxicity Mouse Model.

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, CHA Bundang Medical Center, CHA University.

Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.

出版信息

Otol Neurotol. 2018 Sep;39(8):e731-e737. doi: 10.1097/MAO.0000000000001911.

DOI:10.1097/MAO.0000000000001911

PMID:30015752

Abstract

HYPOTHESIS

We tested whether GV1001 has any ototoxic side effects at different doses and whether it protects hearing in an aminoglycoside-induced ototoxicity mouse model.

BACKGROUND

GV1001, a novel peptide vaccine currently being examined in a Phase 3 clinical trial to treat pancreatic cancer, also has anti-inflammatory and antioxidant effects.

METHODS

In the first experiment, C57/BL6 mice were injected with GV1001 preparations at concentrations of 0.1 to 100 mg/kg for 7 days to evaluate the toxicity of GV1001 on the inner ear and kidneys. In the second experiment, the protective effect of GV1001 was tested in an ototoxicity mouse model that was generated by injecting 800 mg/kg kanamycin (KM) for 2 weeks. The hearing threshold and hair cell loss were compared between the KM + GV1001 group (treated with 10 mg/kg GV1001 for 2 wk) and the KM + saline group. The hearing threshold was measured before, and 7, 14, and 21 days after the initial treatment. The blood urea nitrogen level was measured.

RESULTS

No ototoxicity or renal toxicity was found following treatment with different doses of GV1001 (0.1-100 mg/kg). The KM + saline group showed impaired auditory function and markedly disoriented and missing cochlear hair cells, while the KM + GV1001 group showed significant hearing and hair cell preservation in comparison (p < 0.05).

CONCLUSION

GV1001 itself did not have any detrimental effects on the inner ear or kidney. In the KM induced ototoxicity model, concomitant administration of GV1001 protected against cochlear hair cell damage and preserve hearing.

摘要

假设

我们测试了不同剂量的 GV1001 是否有任何耳毒性副作用，以及它是否在氨基糖苷诱导的耳毒性小鼠模型中保护听力。

背景

GV1001 是一种新型肽疫苗，目前正在进行 3 期临床试验，用于治疗胰腺癌，它还具有抗炎和抗氧化作用。

方法

在第一个实验中，C57/BL6 小鼠连续 7 天注射浓度为 0.1 至 100mg/kg 的 GV1001 制剂，以评估 GV1001 对内耳和肾脏的毒性。在第二个实验中，通过注射 800mg/kg 卡那霉素（KM）2 周建立耳毒性小鼠模型，测试 GV1001 的保护作用。比较 KM+GV1001 组（用 10mg/kg GV1001 治疗 2 周）和 KM+生理盐水组的听力阈值和毛细胞丢失。在初始治疗前、7、14 和 21 天测量听力阈值。测量血尿素氮水平。