Rexin-G是一种无复制能力的逆转录病毒载体，展示了一种隐蔽的SIG结合肽，用于靶向肿瘤中的异常标签（SIG）蛋白，并编码显性阴性的人细胞周期蛋白G1构建体。在此，我们报告了在吉西他滨难治性胰腺腺癌中递增剂量的Rexin-G的安全性和抗肿瘤活性，一个10年的幸存者.对于安全性分析(n=20)，治疗相关的1级不良事件包括疲劳（n=6），寒战(n=2)，头痛（n=1），没有器官损伤也没有DLT.没有病人检测出载体中和抗体呈阳性,抗体gp70，复制型逆转录病毒（RCR），或载体整合到外周血淋巴细胞（PBLs）的基因组DNA中。对于疗效分析(n=15)，一名患者获得完全缓解（CR），两名患者有部分反应（PR），12人病情稳定(SD)。在0-I剂量下，中位无进展生存期（PFS）为2.7、4.0和5.6个月，II,III,分别。剂量0-I时的中位总生存期（OS）和1年OS率分别为4.3个月和0％，在剂量II-III时，它们分别为9.2个月和33.3％。迄今为止,1例患者在接受Rexin-G治疗10年后仍存活,无癌症迹象.一起来看,这些数据表明Rexin-G,第一个靶向基因传递系统，具有独特的安全性并具有显着的抗肿瘤活性，为此，FDA授予了快速通道指定。
Rexin-G is a replication-incompetent retroviral vector displaying a cryptic SIG-binding peptide for targeting abnormal Signature (SIG) proteins in tumors and encoding a dominant-negative human cyclin G1 construct. Herein we report on the safety and antitumor activity of escalating doses of Rexin-G in gemcitabine-refractory pancreatic adenocarcinoma, with one 10-year survivor. For the safety analysis (n = 20), treatment-related grade 1 adverse events included fatigue (n = 6), chills (n = 2), and headache (n = 1), with no organ damage and no DLT. No patient tested positive for vector-neutralizing antibodies, antibodies to gp70, replication-competent retrovirus (RCR), or vector integration into genomic DNA of peripheral blood lymphocytes (PBLs). For the efficacy analysis (n = 15), one patient achieved a complete response (CR), two patients had a partial response (PR), and 12 had stable disease (SD). Median progression-free survival (PFS) was 2.7, 4.0, and 5.6 months at doses 0-I, II, and III, respectively. Median overall survival (OS) and 1-year OS rate at dose 0-I were 4.3 months and 0%, and at dose II-III they were 9.2 months and 33.3%. To date, one patient is still alive with no evidence of cancer 10 years after the start of Rexin-G treatment. Taken together, these data suggest that Rexin-G, the first targeted gene delivery system, is uniquely safe and exhibits significant antitumor activity, for which the FDA granted fast-track designation.
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