Specific Elimination of CD133+ Tumor Cells with Targeted Oncolytic Measles Virus

Abstract

Tumor-initiating cells (TIC) are critical yet evasive targets for the development of more effective antitumoral strategies. The cell surface marker CD133 is frequently used to identify TICs of various tumor entities, including hepatocellular cancer and glioblastoma. Here, we describe oncolytic measles viruses (MV) retargeted to CD133. The viruses, termed MV-141.7 and MV-AC133, infected and selectively lysed CD133 þ tumor cells. Both viruses exerted strong antitumoral effects on human hepatocellular carcinoma growing subcutaneously or multifocally in the peritoneal cavity of nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Notably, the CD133-targeted viruses were more effective in prolonging survival than the parental MV-NSe, which is currently assessed as oncolytic agent in clinical trials. Interestingly, target receptor overexpression or increased spreading kinetics through tumor cells were excluded as being causative for the enhanced oncolytic activity of CD133-targeted viruses. MV-141.7 was also effective in mouse models of orthotopic glioma tumor spheres and primary colon cancer. Our results indicate that CD133-targeted measles viruses selectively eliminate CD133 þ cells from tumor tissue, offering a key tool for research in tumor biology and cancer therapy. Cancer Res; 73(2); 865-74. Ó2013 AACR.

Cancer stem cell vaccine inhibits metastases of primary tumors and induces humoral immune responses against cancer stem cells

“…Several groups have described the generation of CSC-specific CD8 C T cells in vitro; 10,11 the killing of CSCs via non-specific immune cells 12,13 as well as by oncolytic viruses 14 and antibodies. 15 We have reported that CXCR1 blockade selectively targeted human breast CSCs in vitro and in xenografts.…”

Progress in clinical oncolytic virus-based therapy for hepatocellular carcinoma

“…Other engineered pan-cancer-specific OVs have also shown efficacy in preclinical HCC models, including OVs whose genome expression is driven by survivin, an inhibitor of the apoptosis protein family that is overexpressed in the majority of HCC cases (survivin promoter-regulated oncolytic adenovirus vector carrying TP53 gene, AdSurp-P53), and human telomerase reverse transcriptase (hTERT), expressed in up to 90 % of HCCs, but only some 20 % of non-malignant liver cells (hTERT promoter-regulated replicative adenovirus, SG300) (Kannangai et al, 2005; He et al, 2012; Nagao et al, 1999; Liu et al, 2011). More recently, OVs that preferentially target tumour-initiating cells have been engineered, including oncolytic measles virus retargeted to CD133-positive cells (Bach et al, 2013). In the liver, CD133 expression is limited to cancerous tissue, and is associated with colony formation and high proliferative capacity (Kohga et al, 2010;Zhu et al, 2010).…”

Recent Nanomedicine Articles of Outstanding Interest: Functional Nanomaterials for Brain Research Through Advancing Innovative Neurotechnologies Initiative

“…Oncotarget 6 (11), 8788-8806 (2015). Molecular targeting of malignant glioma (GBM), an aggressive terminal brain tumor, is mediated through recognition of cellular receptors presented on the cells surface [7]. Taking into account broad variability of glioma cellular surface markers, exploring the differential expression of proteins on the surface of cancer cells is the key to targeting glioma and therapeutic payloads.…”