干扰素基因刺激蛋白激动剂MSA-2和锰-MSA-2的生殖安全性。
Reproductive safety of STING agonists MSA-2 and manganese-MSA-2.
作者信息
Cai Ya, He Tian, Yang Tao, Li Yating, Yi Lirong, Li Wenqing, Zhou Peng
机构信息
Institute of Reproductive Medicine, School of Medicine, Nantong University, No. 16 Wenfeng Road, Chongchuan District, Nantong 226000, China.
Department of Radiotherapy, Affiliated Hospital of Nantong University, No. 20 Xisi Road, Chongchuan District, Nantong, Jiangsu 226000, China.
出版信息
Toxicol Res (Camb). 2024 Oct 13;13(5):tfae172. doi: 10.1093/toxres/tfae172. eCollection 2024 Oct.
BACKGROUND
MSA-2, as an oral molecule for activating STING signaling pathway to cure the tumor entering clinical trials. The toxicity of MSA-2 has aroused wide concern, especially the reproductive toxicity can not be ignored.
OBJECTIVES
We synthesized the STING agonist (MSA-2) and its derivative manganese-MSA-2 (MSA-2-Mn) and investigated the reproductive toxicity.
METHODS
We evaluated the reproductive effects of MSA-2 and MSA-2-Mn in female mice under the administration alone and on the reproductive system of male mice in the presence or absence of combined radiation.
RESULTS
Results suggested that MSA-2 and MSA-2-Mn have negligible reproductive toxicity in healthy adults. Conclusions: This provides new ideas to enhance the efficacy of immunotherapy, as well as favorable evidence for future systemic dosing in patients of reproductive age and clinical trials of immunotherapy.
背景
MSA-2作为一种激活STING信号通路以治疗肿瘤的口服分子已进入临床试验阶段。MSA-2的毒性已引起广泛关注，尤其是其生殖毒性不容忽视。
目的
合成STING激动剂（MSA-2）及其衍生物锰-MSA-2（MSA-2-Mn），并研究其生殖毒性。
方法
评估MSA-2和MSA-2-Mn单独给药对雌性小鼠的生殖影响，以及在有或无联合辐射情况下对雄性小鼠生殖系统的影响。
结果
结果表明，MSA-2和MSA-2-Mn对健康成年小鼠的生殖毒性可忽略不计。结论：这为提高免疫治疗疗效提供了新思路，也为未来在育龄患者中进行全身给药及免疫治疗临床试验提供了有利证据。
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