Identification of the receptor of oncolytic virus M1 as a therapeutic predictor for multiple solid tumors

Abstract

Over the last decade, oncolytic virus (OV) therapy has shown its promising potential in tumor treatment. The fact that not every patient can benefit from it highlights the importance for defining biomarkers that help predict patients’ responses. As particular self-amplifying biotherapeutics, the anti-tumor effects of OVs are highly dependent on the host factors for viral infection and replication. By using weighted gene co-expression network analysis (WGCNA), we found matrix remodeling associated 8 (MXRA8) is positively correlated with the oncolysis induced by oncolytic virus M1 (OVM). Consistently, MXRA8 promotes the oncolytic efficacy of OVM in vitro and in vivo. Moreover, the interaction of MXRA8 and OVM studied by single-particle cryo-electron microscopy (cryo-EM) showed that MXRA8 directly binds to this virus. Therefore, MXRA8 acts as the entry receptor of OVM. Pan-cancer analysis showed that MXRA8 is abundant in most solid tumors and is highly expressed in tumor tissues compared with adjacent normal ones. Further study in cancer cell lines and patient-derived tumor tissues revealed that the tumor selectivity of OVM is predominantly determined by a combinational effect of the cell membrane receptor MXRA8 and the intracellular factor, zinc-finger antiviral protein (ZAP). Taken together, our study may provide a novel dual-biomarker for precision medicine in OVM therapy.

Rethinking Antigen Source: Cancer Vaccines Based on Whole Tumor Cell/tissue Lysate or Whole Tumor Cell

“…These factors limit the clinical effectiveness of oncolytic viruses in treating gliomas. [ 222 ] However, the study used neural stem cells (NSCs), which can migrate and spread freely within tumors, to deliver a genetically engineered oncolytic adenovirus (CRAd‐S‐pk7) in a first‐in‐human, open‐label, phase 1, dose‐escalation trial. The phase1 trial has proved the safety and tolerability of NSC‐CRAd‐S‐pk7 injection during surgery in patients, considering that the patients had favorable clinical outcomes (in terms of survival).…”

Improving cancer immunotherapy by rationally combining oncolytic virus with modulators targeting key signaling pathways

“…Additionally, Nguyen and colleagues showed that defects in IFN-JAK-STAT pathway as response biomarkers to virotherapy mediated by oncolytic VSV and HSV-1 [ 116 ]. Another recent study identified the receptor of oncolytic alphavirus M1 as a therapeutic predictor for multiple solid tumors [ 117 ]. In summary, we believe that some of these biomarkers are tumor type-specific and/or OV-specific.…”

Review Article: Immune Landscape and Immunotherapy Options in Cervical Carcinoma

“…They have the ability to bind with specific receptors and are then internalized by endocytosis. Oncolytic viruses are a group of viruses that can target and bind to specific receptors, which are overly expressed on cancer cells (CD144, CD46, and CD44) [ 57 ]. Cancer cells have weak or deficient interferon (IFN) pathways, which make them more susceptible to infection with oncolytic virus as compared to normal cells.…”