In situ extended immune activation instantly after tumor resection by oncolytic virus controls postoperative tumor recurrence.

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.