Oncolytic Vaccinia Virus Expressing White-Spotted Charr Lectin Regulates Antiviral Response in Tumor Cells and Inhibits Tumor Growth In Vitro and In Vivo

Abstract

Oncolytic vaccina virus (oncoVV) used for cancer therapy has progressed in recent years. Here, a gene encoding white-spotted charr lectin (WCL) was inserted into an oncoVV vector to form an oncoVV-WCL recombinant virus. OncoVV-WCL induced higher levels of apoptosis and cytotoxicity, and replicated faster than control virus in cancer cells. OncoVV-WCL promoted IRF-3 transcriptional activity to induce higher levels of type I interferons (IFNs) and blocked the IFN-induced antiviral response by inhibiting the activity of IFN-stimulated responsive element (ISRE) and the expression of interferon-stimulated genes (ISGs). The higher levels of viral replication and antitumor activity of oncoVV-WCL were further demonstrated in a mouse xenograft tumor model. Therefore, the engineered oncoVV expressing WCL might provide a new avenue for anticancer gene therapy.

Oncolytic Vaccinia Virus Harboring Aphrocallistes vastus Lectin Inhibits the Growth of Hepatocellular Carcinoma Cells

“…The results showed that oncoVV-AVL exhibited an efficient antitumor effect with a unique immunomodulatory mechanism, that is, inducing the production of type I IFNs while suppressing the ISREmediated viral defense response to promote self-replication. Our results support the idea that arming vaccinia virus with marine lectin can not only enhance the persistence of viral replication but also promote therapeutic efficacy [22].…”

“…The volume of tumor was measured and recorded every five days. Tumor volume (V) was calculated as: V = (length × width 2 )/2 [22].…”

“…Crenomytilus grayanus lectin (CGL) enhanced G2/M cell cycle arrest and induced Burkitt's lymphoma cell apoptosis by interacting with the cellular surface glycan GB3 and the cleavage of poly ADP-ribose polymerase [18]. In addition, Tachypleus tridentatus lectin (TTL) [19], Haliotis discus discus sialic acid binding lectin (HddSBL) [20], Dicentrarchus labrax fucose-binding lectin (DLFBL) [21], Strongylocentrotus purpuratus rhamnose-binding lectin (SpRBL) [21], as well as White-spotted charr lectin (WCL) [22] were inserted into oncolytic virus and displayed cytotoxic effects against multiple cancer cells through inducing apoptosis. These findings show that marine lectins are an important candidate for tumor therapy.…”

The gamble between oncolytic virus therapy and IFN

“…Specifically, blocking the IFN-induced antiviral response is achieved through two pathways. On the one hand, OncoVV-WCL can inhibit the activity of IFN stimulatory response element (ISRE), and on the other hand, inhibition of JAK-STAT signaling pathway by OncoVV-WCL limits ISG expression ( 160 ). By these means, the virus can avoid elimination by the antiviral pathway and thus exert a normal lytic effect ( 160 ).…”

Coming New Age of Marine Glycomics: The Fundamental, Medical, and Ecological Aspects

“…Wang, Zhou, Liu et al demonstrate the construction of a oncoVV-WCL recombinant virus, obtained though the insertion of the white-spotted charr lectin (WCL) gene into an oncolytic vaccinia virus (oncoVV) vector [ 8 ]. WCL is a rhamnose-binding lectin belonging to the SUEL-type lectin family, identified from white-spotted Charr ( Salvelinus leucomaenis ) eggs based on its primary structure.…”