降低自主神经系统的敏感性,以减轻抗GD2单克隆抗体的副作用
Jaume Mora1, Alejandra Climent2, Mònica Roldán3
1Pediatric Cancer Center Barcelona (PCCB), Hospital Sant Joan de Déu, Barcelona, Spain.
反GD2单克隆抗体 (mAbs) 激活自主神经系统 (ANS),在高危神经母细胞瘤 (HR-NB) 患者中引起副作用. 一个新的"Step-Up"输液协议通过利用高血压来最大限度地减少这些副作用.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
背景情况:
- 反GD2单克隆抗体 (mAbs) 提高了高危神经母细胞瘤 (HR-NB) 的存活率.
- 严重的不良事件 (AE),如疼痛,限制了抗GD2 mAb治疗的发展.
- 自主神经系统 (ANS) 激活被认为是这些AE背后的机制.
研究的目的:
- 为了研究人类外周神经中的GD2表达.
- 为了阐明抗GD2 mAb诱导的副作用的机制.
- 开发和测试一种新的输液协议,以减轻AE.
主要方法:
- 同焦点和超分辨率显微镜来评估人类神经上的GD2表达.
- 交感皮肤反应 (SSR) 测试,以评估患者的ANS活性.
- 数学建模和临床测试"一步升级"输液协议.
主要成果:
- GD2在外围神经中的施万细胞上被选择性地表达.
- 反GD2 mAb输液迅速改变了SSR,表明ANS激活.
- 该Step-Up协议减少了副作用,同时保持了药物暴露,与观察到的tachyphylaxis一致.
结论:
- 在人类中,ANS是抗GD2mAbs的主要非瘤点.
- 该Step-Up协议有效地管理了瘤外的目标副作用.
- 通过SSR证明的太基法力学是Step-Up协议成功的关键.
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