在复发性不耐药卵巢癌中使用denileukin diftitox (ONTAK) 进行内免疫疗法
John B Liao1, Nikita S Jejurikar1, Katie M Hitchcock-Bernhardt1
1Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, 1959 NE Pacific St, Seattle, WA 98195, United States of America; UW Medicine Cancer Vaccine Institute, University of Washington, 850 Republican St, Seattle, WA 98195, United States of America.
Gynecologic oncology
|October 3, 2024
概括
素二毒素 (ONTAK) 可以安全地给卵巢癌患者进行腹腔内注射,减少调节性T细胞. 虽然它是安全的,但在这个I期试验中,它没有显著改变瘤相关的细胞因子水平.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
背景情况:
- 调节性T细胞 (Tregs) 与卵巢癌的预后不佳有关.
- 德尼列二毒素 (ONTAK) 是一种研究中的融合蛋白,旨在耗尽Tregs.
研究的目的:
- 为了评估腹膜内拒二毒素 (ONTAK) 在晚期耐火性卵巢癌中的安全性和耐受性.
- 为了评估ONTAK对调节性T细胞和细胞因子的作用,在炎和周围血液中.
主要方法:
- 一期剂量升级研究,招募了10名患有晚期,耐火性卵巢癌的患者.
- 内注射的denileukin diftitox (ONTAK) 在不断升级的剂量 (5,15,25μg/kg).
- 通过CA-125,Treg量化 (RT-PCR) 和细胞因子分析 (Luminex) 评估临床反应.
主要成果:
- 确定的最大耐受剂量为15μg/kg;在一名患者中观察到剂量限制性毒性.
- 大多数不良事件是短暂的 (等级1-2);一名患者经历了25μg/kg的细胞因子风暴.
- 登列二毒素 (ONTAK) 降低了周围血液和炎中的调节性T细胞;没有发现关键细胞因子 (IL-8,TGF-β,sIL2Ra) 的显著变化.
结论:
- 腹腔内排泄素二毒素 (ONTAK) 可以安全地给患有复发性,耐药性卵巢癌的患者使用.
- 治疗有效地减少了外周血液和瘤中的调节性T细胞.
- 在治疗后没有观察到测量细胞因子水平的显著变化.
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