Hartley Marion L, Bade Najeebah A, Prins Petra A, Ampie Leonel, Marshall John L
a The Ruesch Center for the Cure of GI Cancers at the Georgetown Lombardi Comprehensive Cancer Center ; Georgetown University ; Washington , DC USA.
Hum Vaccin Immunother. 2015;11(4):931-7. doi: 10.1080/21645515.2015.1011017.
Although pancreatic cancer is but the eleventh most prevalent cancer in the US, it is predicted that of all the patients newly diagnosed with this disease in 2014, only 27% will still be alive at the end of the first year, which is reduced to 6% after 5 years. The choice of chemotherapy in the treatment of pancreatic cancer is dependent on disease stage and patient performance status but, in general, the most widely used approved regimens include 5-fluorouracil (5-FU) combinations and gemcitabine combinations. Recent therapeutic strategies have resulted in an improvement in survival of patients with pancreatic cancer but the magnitude of change is disappointing and vast improvements are still needed. The goal of immunotherapy is to enhance and guide the body's immune system to recognize tumor-specific antigens and mount an attack against the disease. Among newer immune therapies, GI-4000 consists of 4 different targeted molecular immunogens, each containing a different Ras protein (antigen) encoded by the most commonly found mutant RAS genes in solid tumors-RAS mutations exist in over 90% of pancreatic ductal adenocarcinomas. We will review pancreatic cancer epidemiology and its current treatment options, and consider the prospects of immunotherapy, focusing on GI-4000. We discuss the potential mechanism of action of GI-4000, and the performance of this vaccination series thus far in early phase clinical trials.
尽管胰腺癌在美国仅为第十一大常见癌症,但据预测,2014年所有新诊断出患有这种疾病的患者中,只有27%在第一年末仍存活,5年后这一比例降至6%。胰腺癌治疗中化疗方案的选择取决于疾病分期和患者的身体状况,但一般来说,最广泛使用的获批方案包括5-氟尿嘧啶(5-FU)联合用药和吉西他滨联合用药。最近的治疗策略已使胰腺癌患者的生存率有所提高,但变化幅度令人失望,仍亟需大幅改善。免疫疗法的目标是增强并引导人体免疫系统识别肿瘤特异性抗原并对抗疾病。在较新的免疫疗法中,GI-4000由4种不同的靶向分子免疫原组成,每种都含有由实体瘤中最常见的突变RAS基因编码的不同Ras蛋白(抗原)——超过90%的胰腺导管腺癌存在RAS突变。我们将回顾胰腺癌的流行病学及其当前的治疗选择,并探讨免疫疗法的前景,重点关注GI-4000。我们将讨论GI-4000的潜在作用机制,以及该疫苗系列在早期临床试验中的表现。