Gilliam A D, Watson S A
University of Nottingham, Division of Preclinical Oncology, D Floor, West Block, Queen's Medical Centre, University Hospital, Nottingham, NG7 2UH, UK.
Expert Opin Biol Ther. 2007 Mar;7(3):397-404. doi: 10.1517/14712598.7.3.397.
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.
G17DT（Gastrimmune）是一种抗胃泌素-17免疫原，可产生阻断胃泌素刺激肿瘤生长的抗体。它已完成针对胰腺癌患者的III期试验，并计划开展针对胃癌的III期试验。临床前研究证实，G17DT诱导产生的抗体既能减少胃泌素-17刺激的胃酸分泌，又能抑制胃泌素与胆囊收缩素-2受体相互作用。在多个肿瘤系统中已证实G17DT被动免疫和主动免疫的疗效，在胰腺癌、结肠癌和胃癌模型的联合化疗中显示出相加作用。针对晚期胃肠道恶性肿瘤的I/II期研究表明，G17DT主动免疫未引发全身或自身免疫反应。使用优化的剂量和给药方案产生了高比例的抗体应答者（70%），副作用极小，且在2至4周内可检测到抗体滴度。G17DT联合化疗的II期试验也已在胃癌和结直肠癌中进行。一项针对晚期胰腺癌患者的G17DT与安慰剂对比的III期、多中心、双盲、随机、对照试验通过意向性分析证实G17DT组患者的生存期有所改善。一项针对晚期胰腺癌患者的G17DT联合吉西他滨与安慰剂及吉西他滨对比的随机、双盲、跨国、多中心研究结果显示，除了对高抗体滴度患者的亚组分析外，总体生存期未得到改善。因此，G17DT代表了一种新兴的胃肠道恶性肿瘤治疗新方法。
