A clinical trial with chimeric monoclonal antibody WX-G250 and low dose interleukin-2 pulsing scheme for advanced renal cell carcinoma
A clinical trial with chimeric monoclonal antibody WX-G250 and low dose interleukin-2 pulsing scheme for advanced renal cell carcinoma
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DOI：
10.1016/s0022-5347(05)00040-6
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发表时间：
2006-01-01
影响因子：
6.6
通讯作者：
Mulders, PFA
中科院分区：
文献类型：
--
作者：
Bleumer, I;Oosterwijk, E;Mulders, PFA
目的：WX-G250是一种与碳酸氢酶IXG250/MN结合的嵌合单抗，它存在于95%以上的肾透明细胞亚型肾癌上。建议WX-G250的工作机理为ADCC。由于小剂量白介素2脉冲方案可以增加ADCC效应细胞的激活数量，因此启动了一项多中心研究，以探讨WX-G250联合LD-IL-2能否改善进展性肾细胞癌患者的临床预后。材料和方法：35例进展性透明细胞RCC患者接受WX-G250每周一次的静脉滴注，共11周，同时每日一次的LD-IL-2方案。对患者进行纵向ADCC容量监测。结果：35例患者中有8例(23%)获得了持久的临床益处，其中3例部分缓解，5例稳定在24周或更长时间。中位生存期22个月。总体而言，治疗耐受性良好，毒性小。在治疗期间，效应细胞的数量增加了，但每细胞的裂解能力并没有增加。结论：WX-G250联合LD-IL-2治疗转移性肾癌安全、耐受性好。与WX-G250单一疗法相比，联合疗法有显著的临床益处，在研究开始时有进展性疾病的转移性肾癌患者的中位生存期为22个月。存活率至少与目前使用的细胞因子方案相似，但具有良好的毒性。
Purpose: WX-G250 is a chimeric monoclonal antibody that binds to carbonic anhydrase IXG250/MN, which is present on greater than 95% of RCCs of the clear cell subtype. The suggested working mechanism of WX-G250 is by ADCC. Because the number of activated ADCC effector cells can be increased by a low dose interleukin-2 pulsing schedule, a multicenter study was initiated to investigate whether WX-G250 combined with LD-IL-2 could lead to an improved clinical outcome in patients with progressive RCC.Materials and Methods: A total of 35 patients with progressive clear cell RCC received weekly infusions of WX-G250 for 11 weeks combined with a daily LD-IL-2 regimen. Patients were monitored longitudinally for ADCC capacity. Radiological assessment of metastatic lesions was performed at week 16 and regularly until disease progression.Results: A durable clinical benefit was achieved in 8 of 35 patients (23%), including 3 with a partial response and 5 with stabilization at 24 weeks or greater. Mean survival was 22 months. In general treatment was well tolerated with little toxicity. The number of effector cells increased during treatment but lytic capacity per cell did not increase. ADCC and clinical outcome did not appear to correlate.Conclusions: WX-G250 combined with LD-IL-2 in patients with metastatic RCC is safe and well tolerated. With a substantial clinical benefit and a median survival of 22 months in patients with metastatic RCC who have progressive disease at study entry combination therapy showed increased overall survival compared to WX-G250 monotherapy. Survival was at least similar to that of currently used cytokine regimens but with a favorable toxicity profile.