In situ extended immune activation instantly after tumor resection by oncolytic virus controls postoperative tumor
Ciliang Guo1, Tian Gao2, Bin Xue3
1State Key Laboratory of Pharmaceutical Biotechnology, Department of General Surgery Nanjing Drum Tower Hospital, The Affiliated Hospital of Medical School, Medical School, Nanjing University, Nanjing 210008, China; Jinan Microecological Biomedicine Shandong Laboratory, Building 1, Jinan Medical and Health Science and Technology Innovation Industrial Park, No. 288, Jiqi Road, Huayin District, Jinan City, Shandong Province, China.
Abstract:
Postoperative tumor recurrence represents a major challenge for patients. Oncolytic virus (OV) therapy has attracted increasing attention in recent years. Here, we construct a supramolecular hydrogel enabling extended release of type V oncolytic adenovirus (adv), with hydrogel stability confirmed experimentally. In situ treatment with the adv-loaded hydrogel (adv@Nap gel) instantly after tumor resection efficiently activates the type I interferon pathway, induces innate and adaptive immunity, controls postoperative tumor recurrence and metastasis, and prolongs mouse survival. We verify the ability of instant in situ treatment with adv@Nap gel to inhibit postoperative tumor recurrence. Notably, oncolytic herpes simplex virus or vaccinia virus loaded in Nap gel can also control postoperative tumor recurrence. Thus, hydrogel-loaded OVs that induce extended immune activation represent a paradigm for sustained antitumor immunotherapy, and in situ sustained immune activation initiated during surgery may represent an important and universal treatment guideline.
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