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Non-secreting IL12 expressing oncolytic adenovirus Ad-TD-nsIL12 in recurrent high-grade glioma: a phase I trial

Author

Listed:
  • Weihai Ning

    (Capital Medical University)

  • Xiao Qian

    (Capital Medical University)

  • Louisa Chard Dunmall

    (Queen Mary University of London)

  • Funan Liu

    (The First Hospital of China Medical University)

  • Yuduo Guo

    (Capital Medical University)

  • Shenglun Li

    (Capital Medical University)

  • Dixiang Song

    (Capital Medical University)

  • Deshan Liu

    (Capital Medical University)

  • Lixin Ma

    (Capital Medical University)

  • Yanming Qu

    (Capital Medical University)

  • Haoran Wang

    (Capital Medical University)

  • Chunyu Gu

    (Capital Medical University)

  • Mingshan Zhang

    (Capital Medical University)

  • Yaohe Wang

    (Queen Mary University of London)

  • Shengdian Wang

    (Chinese Academy of Sciences)

  • Hongwei Zhang

    (Capital Medical University)

Abstract

Malignant glioma is a highly fatal central nervous system malignancy with high recurrence rates. Oncolytic viruses offer potential treatment but need improvement in efficacy and safety. Here we describe a phase I, dose-escalating, single arm trial (ChiCTR2000032402) to study the safety of Ad-TD-nsIL12, an oncolytic adenovirus expressing non-secreting interleukin-12, in patients with recurrent high-grade glioma that connects with the ventricular system. Eight patients received intratumoral treatment via stereotaxis or an Ommaya reservoir, with doses ranging from 5 × 109 to 5 × 1010vp. The primary end point was to determine the maximal tolerated dose. Secondary endpoints included toxicity and anti-tumour ability. Minimal adverse events were observed at doses of 5 × 109 and 1 × 1010vp. Grade 3 seizure was observed in two patients from Cohort 3 (5 × 1010vp). Therefore, the maximum tolerated dose was determined to be 1 × 1010vp. Four patients developed hydrocephalus during follow-up. Among them, symptoms in two patients were relieved after placement of a ventriculo-peritoneal shunt, and the other two only showed ventriculomegaly on MRI scan without neurological deterioration. Complete response (according to Response Assessment in Neuro-Oncology Criteria) in one patient, a partial response in one patient and post-treatment infiltrations of CD4+ and CD8 + T cells into the tumour were documented during this trial. In conclusion, Ad-TD-nsIL12 has demonstrated safety and preliminary efficacy in patients with recurrent high-grade glioma.

Suggested Citation

  • Weihai Ning & Xiao Qian & Louisa Chard Dunmall & Funan Liu & Yuduo Guo & Shenglun Li & Dixiang Song & Deshan Liu & Lixin Ma & Yanming Qu & Haoran Wang & Chunyu Gu & Mingshan Zhang & Yaohe Wang & Sheng, 2024. "Non-secreting IL12 expressing oncolytic adenovirus Ad-TD-nsIL12 in recurrent high-grade glioma: a phase I trial," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53041-7
    DOI: 10.1038/s41467-024-53041-7
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    1. Pengju Wang & Xiaozhu Li & Jiwei Wang & Dongling Gao & Yuenan Li & Haoze Li & Yongchao Chu & Zhongxian Zhang & Hongtao Liu & Guozhong Jiang & Zhenguo Cheng & Shengdian Wang & Jianzeng Dong & Baisui Fe, 2017. "Re-designing Interleukin-12 to enhance its safety and potential as an anti-tumor immunotherapeutic agent," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
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