Autoantibodies against the tumour-associated antigen GA733-2 in patients with colorectal carcinoma
Autoantibodies against the tumour-associated antigen GA733-2 in patients with colorectal carcinoma
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DOI：
10.1007/s002620050536
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发表时间：
1999-02-01
影响因子：
5.8
通讯作者：
Mellstedt, H
中科院分区：
文献类型：
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作者：
Mosolits, S;Harmenberg, U;Mellstedt, H
肿瘤相关抗原（TAA）GA 733 -2在大多数人结肠直肠癌细胞上表达为非分泌性表面分子。在过去的十年中，该抗原已被用作被动和主动免疫治疗的靶标。为了确定针对该抗原的自身抗体的发生率，分析了来自1068名结直肠癌患者的血清中天然存在的针对杆状病毒产生的GA 733 - 2 E蛋白的IgG抗体。共有14.5%的患者有针对该抗原的IgG抗体。在519名患者中，在诊断时收集血清，其中15%的患者具有抗GA 733 - 2 E IgG抗体。在晚期Dukes分期患者中，抗体阳性患者的频率有较高的趋势：A期为11%，D期为32%（P = 0.06）。抗体可以在诊断后长达10年内检测到。克罗恩病或溃疡性结肠炎患者（n = 20）未引发抗GA 733 - 2 E抗体。没有健康对照供体（n = 45）具有针对抗原的可检测抗体。GA 733 - 2 E反应性血清IgG的特异性通过显著抑制mAb 17 -1A（最初用于定义GA 733 -2）与GA 733 - 2 E抗原的结合来表示。阳性患者的血清与表达GA 733 -2的人结肠直肠癌细胞系SW 948结合。在目前的患者人群中，抗体的存在与生存率之间没有显著相关性。然而，在结直肠癌患者中针对该肿瘤抗原的自身抗体的高发生率证实了其在人类中的抗原性，并支持使用GA 733 -2抗原作为免疫治疗的靶点。
The tumour-associated antigen (TAA) GA733-2 is expressed as a non-secreted surface molecule on the majority of human colorectal carcinoma cells. The antigen has been used as a target for passive and active immunotherapy during the last decade. To determine the incidence of autoantibodies against this antigen, sera from 1068 patients with colorectal carcinoma were analysed for naturally occurring IgG antibodies against the baculovirus-produced GA733-2E protein. A total of 14.5% of the patients had IgG antibodies against the antigen. In 519 patients, sera were collected at the time of diagnosis and 15% of those patients had anti-GA733-2E IgG antibodies. There was a tendency to a higher frequency of patients with antibodies among those in the advanced Dukes stages: 11% in stage A and 32% in stage D respectively (P = 0.06). Antibodies could be detected for up to 10 years after the diagnosis. Patients with Crohn's disease or colitis ulcerosa (n = 20) did not elicit anti-GA733-2E antibodies. No healthy control donor (n = 45) had detectable antibodies against the antigen. The specificity of GA733-2E-reactive serum IgG was indicated by significant inhibition of mAb17-1A (originally used to define GA733-2) binding to the GA733-2E antigen. Sera of positive patients bound to the GA733-2-expressing human colorectal carcinoma cell line, SW948. No significant correlation was found between the presence of antibodies and survival in the present patient population. However, the high incidence of autoantibodies against this tumour antigen in colorectal carcinoma patients confirms its antigenicity in humans and supports the use of the GA733-2 antigen as a target for immunotherapy.