Delivery and Biosafety of Oncolytic Virotherapy

Abstract

In recent years, oncolytic virotherapy has emerged as a promising anticancer therapy. Oncolytic viruses destroy cancer cells, without damaging normal tissues, through virus self-replication and antitumor immunity responses, showing great potential for cancer treatment. However, the clinical guidelines for administering oncolytic virotherapy remain unclear. Delivery routes for oncolytic virotherapy to patients vary in existing studies, depending on the tumor sites and the objective of studies. Moreover, the biosafety of oncolytic virotherapy, including mainly uncontrolled adverse events and long-term complications, remains a serious concern that needs to be accurately measured. This review provides a comprehensive and detailed overview of the delivery and biosafety of oncolytic virotherapy.

Keywords: biosafety; delivery route; immunotherapy; oncolytic virotherapy; tumor.

Figure 1

Mechanism of oncolytic virotherapy. When oncolytic viruses attack a normal cell, viruses activate JAK-STAT or NF-κB pathways through interaction between TLRs and PAMPs, which induce type I IFN transcription and release. Then, type I IFN activates PKR, which is essential for regulating abnormal cell proliferation and innate cellular antiviral responses. However, when oncolytic viruses attack cancer cells, interferon signaling and PKR activity are inhibited; thus, virus clearance is blocked, enabling virus replication. Following virus replication, most oncolytic viruses can induce cell death, at which time they release not only tumor-associated antigens that can promote an adaptive immune response but also viral PAMPs and additional cellular DAMPs and cytokines. These released molecules recruit antigen-presenting cells (APCs) and promote their maturation, subsequently activating antigen-specific CD4⁺ and CD8⁺ T cell responses, enabling CD8⁺ T cells to expand into cytotoxic effector cells and mediate antitumor immunity.

Figure 2

Main delivery routes of oncolytic virotherapy. (a) Intravenous delivery: When oncolytic viruses are injected into the peripheral vein, they reach tumor lesions in non-specific organs and systems through the circulation system. (b) Intratumoral delivery: When oncolytic viruses are injected into tumors, they have a direct therapeutic effect on the lesion. (c) Intraperitoneal delivery: When oncolytic viruses are injected into the peritoneal cavity, they will be absorbed into the veins of the peritoneum and then reach tumor lesions of some organs or systems through the circulation system, or they will diffuse directly to tumor lesions in the peritoneal cavity.