Ten- year follow- up of a prospective trial for the targeted therapy of gastric cancer with the human monoclonal antibody PAT-SC1
Ten- year follow- up of a prospective trial for the targeted therapy of gastric cancer with the human monoclonal antibody PAT-SC1
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DOI：
10.3892/or.2014.2987
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发表时间：
2014-03-01
期刊：
影响因子：
4.2
通讯作者：
Illert, Bertram
中科院分区：
文献类型：
--
作者：
Hensel, Frank;Timmermann, Wolfgang;Illert, Bertram
全人单克隆抗体PAT-SC 1对命名为CD 55（PAT-SC 1）的CD 55（衰变加速因子）亚型具有特异性。该抗原在大多数（80%）胃癌（GC）中表达，该抗体在体外和体内诱导肿瘤细胞特异性凋亡。因此，PAT-SC 1被认为是有前途的治疗剂。在这里，我们描述了一项在可切除胃癌患者中进行新辅助治疗的学术临床研究的结果。对1997年至2001年期间接受GC治疗的患者进行了CD 55（PAT-SC 1）表达检测。51例检测呈阳性的可切除患者在手术前48小时接受20 mg PAT-SC 1单次给药。他们接受了标准手术，包括胃次全切除术或全胃切除术，并进行了粘液囊切除术、网膜切除术和改良的D2淋巴结切除术，旨在进行R 0切除。本研究的主要终点是评估PAT-SC 1抗体治疗的副作用，并评估组织病理学效应，如肿瘤消退和诱导细胞凋亡。长期生存率是次要终点。根据WHO I级和II级，PAT-SC 1给药似乎是安全的，仅具有可逆的副作用。尽管使用了低剂量的抗体，但81.6%的患者显示出原发性肿瘤内细胞凋亡增加的迹象，60%的患者显示出肿瘤细胞消退的迹象。比较接受PAT-SC 1抗体治疗的R 0切除CD 55（PAT-SC 1）阳性患者与未接受PAT-SC 1治疗的R 0切除CD 55（PAT-SC 1）阳性患者的历史集合的10年生存率，表明接受治疗的患者具有生存获益。此外，在考克斯回归分析中，比较CD 55（PAT-SC 1）阳性组与CD 55（PAT-SC 1）阴性组的患者生存率表明，CD 55（PAT-SC 1）抗原表达是生存率差的独立预测因子。抗体PAT-SC 1可以是治疗具有表达⑶ 55（PAT-SC 1）的GC的患者的有用的附加治疗剂。与根治性标准手术相结合，作为辅助或新辅助免疫抑制剂给予的PAT-SC 1诱导肿瘤细胞凋亡，这可能改善这些患者的存活率。由于人源性及其与CD 55（PAT-SC 1）抗原的特异性结合，PAT-SC 1在本试验中耐受性良好。
The fully human monoclonal antibody PAT-SC1 is specific for an isoform of CD55 (decay-accelerating factor) designated CD55(PAT-SC1). This antigen is expressed in the majority (80%) of gastric cancers (GCs), and the antibody induces tumour cell-specific apoptosis in vitro as well as in vivo. PAT-SC1, therefore, has been deemed promising as a therapeutic agent. Here, we describe the results of an academic clinical study performed in a neoadjuvant setting with resectable GC patients. Patients undergoing treatment for GC between 1997 and 2001 were tested for CD55(PAT-SC1) expression. Fifty-one resectable patients that tested positively received a single administration of 20 mg PAT-SC1 48 h prior to surgery. They underwent standard surgery with either subtotal or total gastrectomy with bursectomy, omentectomy and a modified D2-lymphadenectomy, aimed at R0 resection. Primary endpoints of the present study were to evaluate side-effects of the PAT-SC1 antibody treatment and to evaluate histopathological effects such as tumour regression and induction of apoptosis. Long-term survival was a secondary endpoint. Administration of PAT-SC1 appeared safe with only reversible side-effects according to WHO grade I and II. Despite the low-dose of the antibody, 81.6% of the patients showed signs of increased apoptosis within the primary tumour and 60% showed signs of tumour cell regression. Comparison of the 10-year survival rates of the R0-resected CD55(PAT-SC1)-positive patients treated with the PAT-SC1 antibody with a historical collective of R0-resected CD55(PAT-SC1)-positive patients not treated with PAT-SC1 indicated a survival benefit in the treated patients. Furthermore, comparison of the patient survival of CD55(PAT-SC1)-positive vs. CD55(PAT-SC1)-negative groups suggested that CD55(PAT-SC1) antigen expression is an independent predictor of poor survival in a Cox regression analysis. Antibody PAT-SC1 may be a useful additive therapeutic agent in the treatment of patients with CD55(PAT-SC1)-expressing GCs. In combination with radical standard surgery, PAT-SC1 given as an adjuvant or neoadjuvant immunotherapeutic agent induces apoptosis in tumour cells which may improve survival of these patients. Because of the human origin and its specific binding to the CD55(PAT-SC1) antigen, PAT-SC1 was well tolerated in this trial.