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溶瘤腺病毒介导的细胞毒性和白细胞介素-12基因治疗转移性胰腺癌I期试验的长期随访

Long-Term Follow-Up of Phase I Trial of Oncolytic Adenovirus-Mediated Cytotoxic and Interleukin-12 Gene Therapy for Treatment of Metastatic Pancreatic Cancer.

作者信息

Bhatnagar Aseem Rai, Siddiqui Farzan, Khan Gazala, Pompa Robert, Kwon David, Nyati Shyam

机构信息

Department of Radiation Oncology, Henry Ford Hospital, Detroit, MI 48202, USA.

Department of Medical Oncology, Henry Ford Hospital, Detroit, MI 48202, USA.

出版信息

Biomedicines. 2024 May 11;12(5):1065. doi: 10.3390/biomedicines12051065.

Abstract

The long-term follow-up findings of the phase I trial evaluating the efficacy of oncolytic adenovirus-mediated cytotoxic and interleukin-12 gene therapy in metastatic pancreatic cancer (mPC) seem very promising. The study employed a replication-competent Adenovector in combination with chemotherapy in a dose-escalation format. The trial demonstrated a clinically meaningful median overall survival (OS) benefit, with patients in the highest dose cohort exhibiting an impressive median OS of 18.4 months. This contrasts starkly with patients receiving lower doses who experienced a median OS of 4.8 and 3.5 months, respectively. Remarkably, subject number 10, who received the highest dose, demonstrated an extraordinary survival of 59.1 months, presenting a compelling case for further exploration. Additionally, this patient displayed complete responses in lung and liver metastases, a rare occurrence in mPC treatment. Statistical analyses supported the observed survival benefit. The unprecedented OS results emphasize the potential of this treatment strategy and pave the way for future investigations into this promising gene therapy approach.

摘要

评估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(mPC)疗效的I期试验的长期随访结果似乎非常有前景。该研究采用了一种具有复制能力的腺载体,并与化疗以剂量递增的形式联合使用。试验显示出具有临床意义的中位总生存期(OS)获益,最高剂量组的患者中位OS达到了令人印象深刻的18.4个月。这与接受较低剂量治疗的患者形成了鲜明对比,后者的中位OS分别为4.8个月和3.5个月。值得注意的是,接受最高剂量治疗的第10号受试者生存期长达59.1个月,这为进一步探索提供了有力依据。此外,该患者的肺和肝转移灶出现了完全缓解,这在mPC治疗中较为罕见。统计分析支持了观察到的生存获益。前所未有的OS结果凸显了这种治疗策略的潜力,并为未来对这种有前景的基因治疗方法的研究铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1af/11118039/6db3addb2c3e/biomedicines-12-01065-g001.jpg

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