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

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 (), Shengdian Wang () and Hongwei Zhang ()
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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

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-53041-7

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