Denileukin diftitox (ONTAK) 是一种白喉/IL-2R 融合蛋白，能够消耗外周血中的调节性 T 细胞。局部免疫微环境中的调节性 T 细胞已被证明与卵巢癌的不良预后相关。本研究探讨了denileukin diftitox (ONTAK)是否可以安全地腹腔注射给晚期难治性卵巢癌患者，并评估了其对腹水和外周血中调节性T细胞和肿瘤相关细胞因子的影响。腹膜内denileukin diftitox的I期剂量递增研究（ ONTAK）以 3 个剂量（5 μg/kg、15 μg/kg 和 25 μg/kg）招募了 10 名晚期难治性卵巢癌患者。连续 CA-125 测量评估临床反应。使用 RT-PCR 和 Luminex 测量的细胞因子水平对调节性 T 细胞进行定量。最大耐受剂量为 15 µg/kg，扩展组中 6 名患者中有 1 名观察到剂量限制性毒性。大多数不良事件为 1-2 级暂时性不良事件。一名接受 25 μg/kg 剂量治疗的患者经历了细胞因子风暴并长期住院。 3 名患者治疗后 CA-125 下降，但均未达到部分缓解标准。 Denileukin diftitox (ONTAK) 治疗可减少外周血和腹水中的调节性 T 细胞。接受治疗的患者腹水或外周血中IL-8、TGF-β、sIL2Ra没有出现任何显着变化。Denileukin diftitox (ONTAK)可以安全地腹腔注射给复发难治性卵巢癌患者。腹水和外周血中的调节性 T 细胞减少，但细胞因子水平没有显着变化。ClinicalTrials.gov # NCT00357448。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Denileukin diftitox (ONTAK) is a diphtheria/IL-2R fusion protein able to deplete regulatory T cells in peripheral blood. Regulatory T cells in the local immune microenvironment have been shown to be associated with poor prognosis in ovarian cancer. This study examined whether denileukin diftitox (ONTAK) could be safely administered intraperitoneal in patients with advanced refractory ovarian cancer and assessed its effects on regulatory T cells and tumor associated cytokines in ascites and peripheral blood.A phase I dose escalation study of intraperitoneal denileukin diftitox (ONTAK) enrolled 10 patients with advanced, refractory ovarian carcinoma at 3 doses (5 μg/kg, 15 μg/kg, and 25 μg/kg). Serial CA-125 measurements assessed clinical response. Regulatory T cells were quantified using RT-PCR and cytokine levels measured by Luminex.The maximum tolerated dose was 15 μg/kg with a dose limiting toxicity observed in 1 out of 6 patients in the expansion group. The majority of adverse events were transient grades 1-2. One patient treated at the 25 μg/kg dose experienced cytokine storm with prolonged hospitalization. 3 patients had decreases in CA-125 after treatment but none met criteria for partial response. Treatment with denileukin diftitox (ONTAK) decreased regulatory T cells in peripheral blood and ascites. Treated patients did not show any significant changes in IL-8, TGF-β, sIL2Ra in ascites or peripheral blood.Denileukin diftitox (ONTAK) can be safely administered intraperitoneally to recurrent refractory ovarian cancer patients. Regulatory T cells were reduced in ascites and peripheral blood, but there were no significant changes in cytokine levels.ClinicalTrials.gov # NCT00357448.Copyright © 2024 Elsevier Inc. All rights reserved.