Inhibition of Tumor Metastasis by Liquid Nitrogen-Shocked Tumor Cells with Oncolytic Viruses Infection

Despite the tumor-selective lytic efficacy of oncolytic viruses (OVs), their systemic delivery still faces the challenges of limited circulating periods, poor tumor tropism, and spontaneous antiviral immune responses. Herein, we describe a virus-concealed tumor-targeting strategy enabling OVs delivery toward lung metastasis via systemic administration. The OVs can actively infect, be internalized, and cloak into tumor cells, then the tumor cells are subsequently treated with liquid nitrogen-shocking to eliminate the pathogenicity. Such a Trojan Horse-like vehicle avoids virus neutralization and clearance in the bloodstream and facilitates tumor-targeted delivery for more than 110-fold virus enrichment in the tumor metastasis. In addition, this strategy can serve as a tumor vaccine and initiate endogenous adaptive anti-tumor effects through increasing the memory subtypes of T cells and modulating the tumor immune microenvironment, including reducing the M2 macrophage, downregulating Treg cells and augmenting T cells’ priming. This article is protected by copyright. All rights reserved