Adenovirus vector carrying REIC/DKK-3 gene: neoadjuvant intraprostatic injection for high-risk localized prostate cancer undergoing radical prostatectomy.
Adenovirus vector carrying REIC/DKK-3 gene: neoadjuvant intraprostatic injection for high-risk localized prostate cancer undergoing radical prostatectomy.
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DOI：
10.1038/cgt.2016.53
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发表时间：
2016-11
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
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作者：
作为使用携带人REIC（永生化细胞表达减少）/Dkk-3基因（Ad-REIC）的腺病毒载体进行原位基因治疗的首次人体研究，我们对接受根治性前列腺切除术（RP）的高危局限性前列腺癌患者进行了新辅助前列腺内注射。RP后5年内复发概率为35%或更高的患者（根据Kendall列线图计算）入选。患者每隔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。在确认最初计划的三种递增剂量（1.0-1.2 ml中的1.0 × 1010、1.0 × 1011和1.0 × 1012病毒颗粒（vp））治疗干预的安全性后（n=3、3和6），进一步研究了额外的更高剂量（3.6 ml中的3.0 × 1012 vp）（n=6）。所有四种DL（包括额外剂量水平-4（DL-4））均可行，除1级或2级一过性发热外，无不良事件。实验室毒性为1级或2级天冬氨酸转氨酶/丙氨酸转氨酶升高（n=4）。关于抗肿瘤活性，以明确的剂量依赖性方式检测到细胞病变效应（肿瘤变性伴细胞溶解和固缩）和靶向肿瘤区域中的显著肿瘤浸润淋巴细胞。因此，DL-4的生化无复发生存率明显优于患者组DL-1+2+3。
As the First-In-Human study of in situ gene therapy using an adenovirus vector carrying the human REIC (reduced expression in immortalized cell)/Dkk-3 gene (Ad-REIC), we conducted neoadjuvant intraprostatic injections in patients with high-risk localized prostate cancer undergoing radical prostatectomy (RP). Patients with recurrence probability of 35% or more within 5 years following RP, as calculated by Kattan's nomogram, were enrolled. Patients received two ultrasound-guided intratumoral injections at 2-week intervals, followed by RP 6 weeks after the second injection. After confirming the safety of 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. All four DLs including the additional dose level-4 (DL-4) were feasible with no adverse events, except for grade 1 or 2 transient fever. Laboratory toxicities were grade 1 or 2 elevated aspartate transaminase/alanine transaminase (n=4). Regarding antitumor activities, cytopathic effects (tumor degeneration with cytolysis and pyknosis) and remarkable tumor-infiltrating lymphocytes in the targeted tumor areas were detected in a clear dose-dependent manner. Consequently, biochemical recurrence-free survival in DL-4 was significantly more favorable than in patient groups DL-1+2+3.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
10.3
作者：
Kattan, MW;Eastham, JA;Scardino, PT
通讯作者：
Scardino, PT
影响因子：
6.4
作者：
通讯作者：
--
DOI：
10.1084/jem.20050915
发表时间：
2005-12-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Casares N;Pequignot MO;Tesniere A;Ghiringhelli F;Roux S;Chaput N;Schmitt E;Hamai A;Hervas-Stubbs S;Obeid M;Coutant F;Métivier D;Pichard E;Aucouturier P;Pierron G;Garrido C;Zitvogel L;Kroemer G
通讯作者：
Kroemer G
影响因子：
6.6
作者：
Klotz, LH;Goldenberg, SL;Chatterjee, S
通讯作者：
Chatterjee, S