A phase II study of a 5T4 oncofoetal antigen tumour-targeted superantigen (ABR-214936) therapy in patients with advanced renal cell carcinoma.
A phase II study of a 5T4 oncofoetal antigen tumour-targeted superantigen (ABR-214936) therapy in patients with advanced renal cell carcinoma.
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DOI：
10.1038/sj.bjc.6603567
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发表时间：
2007-02-26
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
在一项II期研究中，43名肾细胞癌患者接受了个体化剂量的ABR-214936治疗；将识别抗原5T4的Fab与葡萄球菌肠毒素a融合，连续4天静脉注射药物，1个月后重复治疗。治疗伴有中度发热和恶心，但耐受性良好。在40名可评估的患者中，28名患者在2个月时疾病得到控制，4个月时，1名患者出现部分缓解（PR）， 16名患者病情稳定。最小随访26个月的中位生存期为19.7个月，至今有13例患者存活。与公布的预期相比，mozer预后标准的分层突出了延长的生存期。接受较高药物暴露的患者有更好的疾病控制，寿命几乎是预期的两倍，而低药物暴露的患者则存活了下来。反复注射后持续的白细胞介素-2 （IL-2）产生似乎是临床效果的生物标志物，因为治疗第2天诱导的IL-2水平与生存率相关。疾病的高度控制和较长的生存期表明这种治疗是有效的。这些发现将用于下一代药物的试验设计，降低抗原性和毒性。
In a phase II study, 43 renal cell carcinoma patients were treated with individualised doses of ABR-214936; a fusion of a Fab recognising the antigen 5T4, and Staphylococcal enterotoxin A. Drug was given intravenously on 4 consecutive days, treatment was repeated 1 month later. Treatment was associated with moderate fever and nausea, but well tolerated. Of 40 evaluable patients, 28 had disease control at 2 months, and at 4 months, one patient showed partial response (PR) and 16 patients stable disease. Median survival, with minimum follow-up of 26 months was 19.7 months with 13 patients alive to date. Stratification by the Motzer's prognostic criteria highlights prolonged survival compared to published expectation. Patients receiving higher drug exposure had greater disease control and lived almost twice as long as expected, whereas the low-exposure patients survived as expected. Sustained interleukin-2 (IL-2) production after a repeated injection appears to be a biomarker for clinical effect, as the induced-IL-2 level on the day 2 of treatment correlated with survival. The high degree of disease control and the prolonged survival suggest that this treatment can be effective. These findings will be used in the trial design for the next generation of drug, with reduced antigenicity and toxicity.
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影响因子：
8.8
作者：
Forsberg, G;Ohlsson, L;Brodin, T;Bjork, P;Lando, P A;Shaw, D;Stern, P L;Dohlsten, M
通讯作者：
Dohlsten, M
影响因子：
6.4
作者：
HOLE, N;STERN, PL
通讯作者：
STERN, PL
影响因子：
8.8
作者：
HOLE, N;STERN, PL
通讯作者：
STERN, PL
影响因子：
45.3
作者：
Motzer, RJ;Michaelson, MD;Rini, BI
通讯作者：
Rini, BI
影响因子：
5.6
作者：
Erlandsson, E;Andersson, K;Forsberg, G
通讯作者：
Forsberg, G