In situ extended immune activation instantly after tumor resection by oncolytic virus controls postoperative tumor recurrence
Ciliang Guo, Tian Gao, Bin Xue, Louqian Zhang, Shuo Wang, Rongrong Xiao, Lingkai Kong, Yuxin Zhang, Qilei Xin, Yi Cao, Xiaosong Gu, Chunping Jiang, Junhua Wu
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.