在口腔恶性黑色素瘤中化PD-1单克隆抗体:疗效和探索性生物标志物分析
Masaya Igase1,2,3, Kenji Hagimori4,5, Sakuya Inanaga1
1Laboratory of Molecular Diagnostics and Therapeutics, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.
Journal for immunotherapy of cancer
|January 22, 2026
概括
这项研究表明,化抗PD-1抗体治疗 (ca-4F12-E6) 在患有口腔恶性黑色素瘤 (OMM) 的狗中具有持久的抗瘤活性. 基线炎症和微卫星不稳定性 (MSI) 可能预测治疗成功,支持OMM作为人类免疫瘤学的模型.
科学领域:
- 兽医瘤学 兽医瘤学
- 免疫治疗是一种免疫疗法.
- 翻译研究是翻译研究.
背景情况:
- 狗的口腔恶性黑色素瘤 (OMM) 是积极的,具有有限的持久治疗反应.
- 狗OMM作为人类粘膜黑色素瘤免疫疗法研究的宝贵模型.
- 在犬类OMM中缺乏对抗编程细胞死亡蛋白1 (PD-1) 治疗的预测生物标志物.
研究的目的:
- 评估在患有高级OMM的狗中使用犬化抗PD-1抗体 (ca-4F12-E6) 的安全性和有效性.
- 在接受免疫治疗的狗OMM患者中确定治疗反应和生存的预测生物标志物.
主要方法:
- 一个多中心临床试验,涉及150只以ca-4F12-E6.6治疗的高级OMM的狗.
- 使用cRECIST V.1.0.0.使用治疗反应的评估.
- 综合生物标记分析包括血液参数,细胞因子,淋巴细胞子集,微卫星不稳定性 (MSI) 和瘤RNA测序.
主要成果:
- 总体响应率为14.7%,最佳总体响应率为16.7%.
- 基线炎症标志物 (白细胞,中性粒细胞,C反应蛋白) 的增加与较差的结果相关.
- 微卫星不稳定性高 (MSI高) 瘤与显著更长的整体存活率 (OS) 相关.
结论:
- 化抗PD-1抗体 (ca-4F12-E6) 在犬类OMM中表现出持久的抗瘤活性和可管理的安全性.
- 基线系统性炎症和MSI状态是犬类OMM临床结果的潜在预测生物标志物.
- 狗OMM是人类免疫瘤学和生物标志物发现的相关比较模型.
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