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Re-designing Interleukin-12 to Enhance Its Safety and Potential as an Anti-Tumor Immunotherapeutic Agent

Re-designing Interleukin-12 to Enhance Its Safety and Potential as an Anti-Tumor Immunotherapeutic Agent

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 Feng, Louisa S Chard, etc.

Nat Commun. 2017 Nov 9;8(1):1395.

PMID: 29123084

Abstract:

Interleukin-12 (IL-12) has emerged as one of the most potent agents for anti-tumor immunotherapy. However, potentially lethal toxicity associated with systemic administration of IL-12 precludes its clinical application. Here we redesign the molecule in such a way that its anti-tumor efficacy is not compromised, but toxic effects are eliminated. Deletion of the N-terminal signal peptide of IL-12 can effect such a change by preventing IL-12 secretion from cells. We use a newly designed tumor-targeted oncolytic adenovirus (Ad-TD) to deliver non-secreting (ns) IL-12 to tumor cells and examine the therapeutic and toxic effects in Syrian hamster models of pancreatic cancer (PaCa). Strikingly, intraperitoneal delivery of Ad-TD-nsIL-12 significantly enhanced survival of animals with orthotopic PaCa and cured peritoneally disseminated PaCa with no toxic side effects, in contrast to the treatment with Ad-TD expressing unmodified IL-12. These findings offer renewed hope for development of IL-12-based treatments for cancer.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1431724309	PACA		1431724-30-9	Price

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