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

Despite the superior tumor 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, a virus-concealed tumor-targeting strategy enabling OVs' delivery toward lung metastasis via systemic administration is described. 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 antitumor effects through increasing the memory T cells and modulating the tumor immune microenvironment, including reducing the M2 macrophage, downregulating Treg cells, and priming T cells.

Automated summary

This study describes a virus-concealed tumor-targeting strategy that enables the delivery of oncolytic viruses (OVs) to lung metastasis through systemic administration. The OVs can actively infect, be internalized, and cloak into tumor cells, which are subsequently treated to eliminate their pathogenicity. This Trojan Horse-like vehicle avoids virus neutralization and clearance in the bloodstream and facilitates tumor-targeted delivery with over 110-fold virus enrichment. Additionally, this strategy can function as a tumor vaccine and initiate endogenous adaptive antitumor effects by increasing memory T cells and modulating the tumor immune microenvironment.