A phase I clinical trial of oncolytic adenovirus mediated suicide and interleukin-12 gene therapy in patients with recurrent localized prostate adenocarcinoma.
A phase I clinical trial of oncolytic adenovirus mediated suicide and interleukin-12 gene therapy in patients with recurrent localized prostate adenocarcinoma.
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DOI：
10.1371/journal.pone.0291315
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
在一项I期剂量递增和安全性研究中（NCT 02555397），一种表达yCD、TK和hIL-12的可复制溶瘤腺病毒在15名患有局部复发性前列腺癌（T1 c-T2）的受试者中以增加的剂量施用Ad 5-yCD/mutTKSR 39 rep-hIL-12（1 × 1010至1 × 1012个病毒颗粒），随后用5-氟胞嘧啶（5-FC）和缬更昔洛韦（vGCV）处理7天。主要终点是第30天的毒性，而次要和探索性终点是IL-12、IFNγ、CXCL 10和外周血单核细胞（PBMC）的定量。未达到研究最大耐受剂量（MTD），表明1012个病毒颗粒是安全的。共观察到115起不良事件，其中大多数（92%）为1/2级，不需要任何治疗。仅在2例患者中检测到腺病毒DNA。分别在57%、93%和79%的患者中观察到IL-12、IFNγ和CXCL 10升高。血清细胞因子表现出病毒剂量依赖性，在最高剂量队列中尤其明显。PBMC分析揭示了第5组基因治疗后的免疫系统活化。治疗前后PSA倍增时间（PSADT）的中位数为1.55年vs 1.18年。该试验证实，当局部施用至前列腺肿瘤时，具有复制能力的Ad 5-IL-12腺病毒（Ad 5-yCD/mutTKSR 39 rep-hIL-12）耐受良好。
In a phase I dose escalation and safety study (NCT02555397), a replication-competent oncolytic adenovirus expressing yCD, TK and hIL-12 (Ad5-yCD/mutTKSR39rep-hIL-12) was administered in 15 subjects with localized recurrent prostate cancer (T1c-T2) at increasing doses (1 × 1010, to 1 × 1012 viral particles) followed by 7-day treatment of 5-fluorocytosine (5-FC) and valganciclovir (vGCV). The primary endpoint was toxicity through day 30 while the secondary and exploratory endpoints were quantitation of IL-12, IFNγ, CXCL10 and peripheral blood mononuclear cells (PBMC). The study maximum tolerated dose (MTD) was not reached indicating 1012 viral particles was safe. Total 115 adverse events were observed, most of which (92%) were grade 1/2 that did not require any treatment. Adenoviral DNA was detected only in two patients. Increase in IL-12, IFNγ, and CXCL10 was observed in 57%, 93%, and 79% patients, respectively. Serum cytokines demonstrated viral dose dependency, especially apparent in the highest-dose cohorts. PBMC analysis revealed immune system activation after gene therapy in cohort 5. The PSA doubling time (PSADT) pre and post treatment has a median of 1.55 years vs 1.18 years. This trial confirmed that replication-competent Ad5-IL-12 adenovirus (Ad5-yCD/mutTKSR39rep-hIL-12) was well tolerated when administered locally to prostate tumors.
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溶瘤腺病毒介导的细胞毒性和白细胞介素-12 基因疗法治疗转移性胰腺癌的 I 期试验。
DOI：
10.1016/j.omto.2020.11.006
发表时间：
2021-03-26
期刊：
Molecular therapy oncolytics
影响因子：
--
作者：
Barton KN;Siddiqui F;Pompa R;Freytag SO;Khan G;Dobrosotskaya I;Ajlouni M;Zhang Y;Cheng J;Movsas B;Kwon D
通讯作者：
Kwon D
影响因子：
5.9
作者：
Roberts, Calpurnyia B.;Albertsen, Peter C.;Lu-Yao, Grace L.
通讯作者：
Lu-Yao, Grace L.
影响因子：
7
作者：
Restifo NP;Gattinoni L
通讯作者：
Gattinoni L
影响因子：
7.7
作者：
Lee, Jong-Chan;Shin, Dong Woo;Hwang, Jin-Hyeok
通讯作者：
Hwang, Jin-Hyeok
影响因子：
12.4
作者：
Freytag, Svend O.;Stricker, Hans;Kim, Jae Ho
通讯作者：
Kim, Jae Ho