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

Abstract

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.

Enhancing the Antitumor Efficacy of Oncolytic Adenovirus Through Sonodynamic Therapy-Augmented Virus Replication

“…After intratumoral administration of oncolytic viruses, a desirable outcome is the transport of tumor-associated antigens released from tumor fragments to the nearby tumor-draining lymph nodes (TDLNs). 5 Within these lymph nodes, dendritic cells (DCs) play a crucial role in processing these antigens, leading to potent stimulation of DC maturation and presentation of the antigens to T cells, which ultimately initiates a robust antitumor immune response. 1 In light of this, our subsequent investigation aimed to determine whether the combination of saOAs plus SDT could effectively prime a strong immunity in melanoma models.…”

Harnessing adenovirus in cancer immunotherapy: evoking cellular immunity and targeting delivery in cell-specific manner

“…This approach induces both a local inflammatory response and a systemic immune response, characterized by an increase in the number of circulating CD25 + and DR + CD3 + T cells and specific antitumor responses [ 194 ]. Likewise, cryoshocked tumor cells, which constitute an OAV reservoir, can eliminate viral proliferation and pathogenicity, steadily release viruses and efficiently initiate an endogenous antitumor response by increasing memory T cells and modulating the TME [ 195 , 196 ]. More recently, extracellular vesicles derived from OAV-infected tumor cells have been used for delivering immunogenic OAV, inducing systemic immune responses through proinflammatory cytokines, and inhibiting primary and metastatic cancers [ 77 , 78 ].…”

Emerging delivery strategy for oncolytic virotherapy

“…Therefore, a recent study has proposed the use of liquid nitrogen shock treatment on tumor cells to eliminate the pathogenicity of the tumor cell carrier while preserving its infectivity and activity. 157 …”