Erythrocyte‐Leveraged Oncolytic Virotherapy (ELeOVt): Oncolytic Virus Assembly on Erythrocyte Surface to Combat Pulmonary Metastasis and Alleviate Side Effects

Abstract

Despite being a new promising tool for cancer therapy, intravenous delivery of oncolytic viruses (OVs) is greatly limited by poor tumor targeting, rapid clearance in the blood, severe organ toxicity, and cytokine release syndrome. Herein, a simple and efficient strategy of erythrocyte‐leveraged oncolytic virotherapy (ELeOVt) is reported, which for the first time assembled OVs on the surface of erythrocytes with up to near 100% efficiency and allowed targeted delivery of OVs to the lung after intravenous injection to achieve excellent treatment of pulmonary metastases while greatly improving the biocompatibility of OVs as a drug. Polyethyleneimine (PEI) as a bridge to assemble OVs on erythrocytes also played an important role in promoting the transfection of OVs. It is found that ELeOVt approach significantly prolonged the circulation time of OVs and increased the OVs distribution in the lung by more than tenfold, thereby significantly improving the treatment of lung metastases while reducing organ and systemic toxicity. Taken together, these findings suggest that the ELeOVt provides a biocompatible, efficient, and widely available approach to empower OVs to combat lung metastasis.

Emerging delivery strategy for oncolytic virotherapy

“…ELeOVt extended the circulation time of OVs after intravenous injection and boosted the transduction efficiency of OVs into tumor cells, demonstrating notable therapeutic efficacy in a murine cancer model with lung metastasis. 166 Other research has reported a chimeric entity of engineered OAs and tumor-specific T cells (including T cell receptor T and CAR-T cells). First, OAs were encapsulated within cell membranes containing tumor-specific antigens (including tumor cells and engineered 293T cells) through lipid squeezing to obtain M@eOA.…”

Enhancing cancer therapy: the integration of oncolytic virus therapy with diverse treatments

“…Moreover, safety concerns are another significant issue. The immune activation triggered by OVs can sometimes lead to an excessive inflammatory response, known as a cytokine storm, which can be harmful or even fatal [ 74 , 75 ]. Regulatory and manufacturing challenges also pose significant barriers.…”