Feasibility of Neoadjuvant Ad-REIC Gene Therapy in Patients with High-Risk Localized Prostate Cancer Undergoing Radical Prostatectomy.
Feasibility of Neoadjuvant Ad-REIC Gene Therapy in Patients with High-Risk Localized Prostate Cancer Undergoing Radical Prostatectomy.
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DOI：
10.1111/cts.12362
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发表时间：
2015-12
期刊：
影响因子：
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通讯作者：
Nasu Y
中科院分区：
文献类型：
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作者：
Kumon H;Sasaki K;Ariyoshi Y;Sadahira T;Araki M;Ebara S;Yanai H;Watanabe M;Nasu Y
在一项使用携带人REIC/Dkk-3基因的腺病毒载体（Ad‐REIC）进行原位基因治疗的I/IIa期研究中，我们评估了高危局限性前列腺癌（PCa）患者根治性前列腺切除术（RP）后癌症复发的抑制作用。在完成最初计划的三种递增剂量（1.0 × 1010、1.0 × 1011和1.0 × 1012病毒颗粒（VP）/1.0-1.2 mL）（n = 3、3和6）的治疗干预后，进一步研究了额外的更高剂量（3.0 × 1012 VP/3.6 mL）（n = 6）。根据Kendall列线图计算，RP后5年内复发概率为35%或以上的患者入选。他们每隔2周接受两次超声引导的瘤内注射，然后在第二次注射后6周接受RP。根据MRI和活检定位的结果，通常，对最初的12名患者给予最突出的癌症区域的一个轨迹注射，并对另外6名患者的多个癌症区域进行3个轨迹注射。与前一组相比，后者的生化无复发生存期显示出显著有利的结局。新辅助Ad-REIC介导同时诱导癌症选择性细胞凋亡和增强抗肿瘤免疫，是预防RP后癌症复发的可行方法。（199）
In a phase I/IIa study of in situ gene therapy using an adenovirus vector carrying the human REIC/Dkk‐3 gene (Ad‐REIC), we assessed the inhibitory effects of cancer recurrence after radical prostatectomy (RP), in patients with high risk localized prostate cancer (PCa). After completing the therapeutic interventions with initially planned three escalating doses of 1.0 × 1010, 1.0 × 1011, and 1.0 × 1012 viral particles (VP) in 1.0–1.2 mL (n = 3, 3, and 6), an additional higher dose of 3.0 × 1012 VP in 3.6 mL (n = 6) was further studied. Patients with recurrence probability of 35% or more within 5 years after RP as calculated by Kattan's nomogram, were enrolled. They received two ultrasound‐guided intratumoral injections at 2‐week intervals, followed by RP 6 weeks after the second injection. Based on the findings of MRI and biopsy mapping, as a rule, one track injection to the most prominent cancer area was given to initial 12 patients and 3 track injections to multiple cancer areas in additional 6 patients. As compared to the former group, biochemical recurrence‐free survival of the latter showed a significantly favorable outcome. Neoadjuvant Ad‐REIC, mediating simultaneous induction of cancer selective apoptosis and augmentation of antitumor immunity, is a feasible approach in preventing cancer recurrence after RP. (199)