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首页> 外文期刊>Expert opinion on biological therapy >G17DT: an antigastrin immunogen for the treatment of gastrointestinal malignancy.
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G17DT: an antigastrin immunogen for the treatment of gastrointestinal malignancy.

机译：G17DT：抗胃泌素免疫原，用于治疗胃肠道恶性肿瘤。

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G17DT (Gastrimmune) is an antigastrin-17 immunogen, raising antibodies that blockade gastrin-stimulated tumor growth. It has completed Phase III trials in patients with pancreatic cancer, and Phase III trials in gastric cancer are planned. Preclinical studies have confirmed that the G17DT-induced antibodies both reduce gastrin-17-stimulated gastric acid secretion and inhibit gastrin from interacting with the cholecystokinin-2 receptor. The efficacy of both passive and active immunization with G17DT has been established in a number of tumor systems, with additive effects demonstrated in combination chemotherapy in pancreatic, colon and gastric tumor models. Phase I/II studies in advanced gastrointestinal malignancies have shown no systemic or autoimmune reactions to active immunization with G17DT. The use of an optimized dose and dosing schedule has yielded a high proportion of antibody responders (70%), with minimal side effects and antibody titers measurable within 2 - 4 weeks. Phase II trials of G17DT in combination with chemotherapy have also been conducted in gastric and colorectal cancer. A Phase III, multicenter, double-blind, randomized, controlled trial of G17DT versus placebo in patients with advanced pancreatic cancer confirmed improved survival of patients in the G17DT group through an intention-to-treat analysis. The results of a randomized, double-blind, multinational, multicenter study of G17DT in combination with gemcitabine versus placebo and gemcitabine in patients with advanced pancreatic cancer failed to show improved overall survival except on subset analysis of patients with high antibody titers. Therefore, G17DT represents an emerging new modality for gastrointestinal malignancy.
机译：G17DT（Gastrimmune）是一种抗胃泌素17免疫原，其产生的抗体可阻断胃泌素刺激的肿瘤生长。它已经完成了对胰腺癌患者的III期试验，并计划在胃癌中进行III期试验。临床前研究已经证实，G17DT诱导的抗体既减少胃泌素17刺激的胃酸分泌，又抑制胃泌素与胆囊收缩素2受体相互作用。已经在许多肿瘤系统中确立了用G17DT进行被动和主动免疫的功效，在胰腺癌，结肠癌和胃癌模型中联合化疗证明了累加作用。在晚期胃肠道恶性肿瘤中的I / II期研究表明，对于G17DT的主动免疫，没有全身或自身免疫反应。优化剂量和给药方案的使用产生了很高比例的抗体应答剂（70％），且副作用最小且可在2-4周内测量出抗体滴度。 G17DT联合化疗的II期临床试验也已在胃癌和大肠癌中进行。 G17DT与安慰剂在晚期胰腺癌患者中进行的III期，多中心，双盲，随机对照试验证实，通过意向性治疗分析，G17DT组患者的生存期得到了改善。 G17DT联合吉西他滨与安慰剂和吉西他滨治疗晚期胰腺癌的随机，双盲，多国，多中心研究结果未能显示总生存期有所改善，除非对高抗体滴度的患者进行了亚组分析。因此，G17DT代表了胃肠道恶性肿瘤的一种新兴形式。

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