Intraprostatic distribution and long-term follow-up after AdV-tk immunotherapy as neoadjuvant to surgery in patients with prostate cancer.
Intraprostatic distribution and long-term follow-up after AdV-tk immunotherapy as neoadjuvant to surgery in patients with prostate cancer.
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DOI：
10.1038/cgt.2013.56
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发表时间：
2013-11
影响因子：
6.4
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中科院分区：
文献类型：
--
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在墨西哥蒙特雷进行了一项I-II期研究，以评估根治性前列腺癌切除术前新诊断的前列腺癌患者的基因介导的细胞毒性免疫治疗。为了研究腺病毒向前列腺的递送，将荧光标记的载体注射到新鲜的前列腺切除标本中，并视觉分析分布。然后，使用最佳体积和部位滴注，经直肠超声引导下前列腺内注射10例腺癌根治术患者。每只动物接受2次顶侧和2次基底侧0.5 ml AdV-tk注射，共1×1011 vp，随后接受14天前体药物治疗。9例患者继续肿瘤切除：6例高危，1例中度和2例低危。从四名患者的切除组织中分析体内载体分布。监测患者的肿瘤进展以及急性和长期安全性。0.5ml的两次顶端和两次基底注射导致腺病毒载体离体和体内的最佳器官范围分布。PSA和肿瘤组织学的一过性升高证明了细胞毒性。在中位随访11.3年后，没有与治疗相关的显著不良事件，也没有晚期毒性。所有6例高危患者均有手术切缘阳性，1例有精囊受累。尽管这些患者中有3例术后PSA缓慢升高，但均未发生转移。中度和低风险患者完全切除，无进展。体内经直肠超声引导的腺病毒载体滴入前列腺的四个部位是实用的门诊手术，耐受性良好，并导致整个前列腺内肿瘤块的分布。AdV-tk没有表现出显著的急性或晚期毒性。PSA和疾病进展的趋势传达了针对残留疾病的持续免疫应答的可能性。
A phase I-II study to evaluate gene mediated cytotoxic immunotherapy in newly diagnosed prostate cancer before radical prostatectomy was conducted in Monterrey, Mexico. To investigate delivery of adenovirus to the prostate, fluorescently labeled vector was injected into fresh prostatectomy specimens and distribution visually analyzed. The optimal volume and site instillation was then used for transrectal ultrasound guided intraprostatic injection in 10 patients with adenocarcinoma scheduled for radical prostatectomy. Each received 2-apical and 2-basal 0.5 ml injections of AdV-tk for a total of 1×1011 vp followed by 14 days of prodrug. Nine patients continued to tumor resection: 6 high-risk, 1 intermediate and 2 low-risk. In-vivo vector distribution was analyzed from resected tissue of four patients. Patients were monitored for tumor progression and acute and long-term safety. Two apical and two basal injections of 0.5ml led to optimal organ-wide distribution of an adenoviral vector ex-vivo and in-vivo. Cytotoxicity was evidenced by transient rise in PSA and tumor histology. There were no significant adverse events deemed related to the treatment and no late toxicities after median follow up of 11.3 years. All six high-risk patients had positive surgical margins and one had seminal vesicle involvement. Despite slow PSA rise post-surgery in 3 of these patients, none developed metastases. The intermediate and low-risk patients had complete resections and none have progressed. In-vivo transrectal ultrasound guided instillation of an adenoviral vector into four sites in the prostate was practical as an outpatient procedure, well tolerated and led to distribution throughout the intraprostatic tumor mass. AdV-tk demonstrated no significant acute or late toxicities. Trends in PSA and disease progression conveyed the possibility of a sustained immune response against residual disease.
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