Oncolytic measles virus strains in the treatment of gliomas

Abstract

Background: Recurrent gliomas have a dismal outcome despite use of multimodality treatment including surgery, radiation therapy and chemotherapy.

Objective: In this article the authors discuss potential applications of oncolytic measles virus strains as novel antitumor agents in the treatment of gliomas.

Methods: Important aspects of measles virus development as an anticancer therapeutic agent including engineering, retargeting and combination studies with other therapeutic modalities are discussed. The translational process that led to the first clinical trial of an engineered measles virus derivative in patients with recurrent glioblastoma multiforme is also described.

Results/conclusions: Oncolytic measles virus strains hold promise as novel antitumor agents in the treatment of gliomas.

Figure 1. A schematic representation of recombinant MV-Edm with soluble human CEA cDNA inserted as an additional transcription unit

CEA: Carcinoembryonic antigen; F: Fusion; H: Hemagglutinin; L: Polymerase proteins; M: Matrix; MV: Measles virus; N: Nucleocapsid; P: Phosphoprotein.

Figure 2. A-J, MV-CEA infection results in prominent syncytia formation in U87, U251, and U118 cells and the primary glioma lines GBM5 and 6

Crystal violet stain, (×200 magnification). A, C, E, G, and I, uninfected U87, U251, U118 cells, GBM5 and 6, respectively. B, D, F, H and J, 72 h after infection of U87, U251, U118, GBM5 and GBM6 cell, respectively, with MV-CEA (MOI 0.1). Extensive syncytia formation is observed preceding cell death. CEA: Carcinoembryonic antigen; GBM: Glioblastoma multiforme; MV: Measles virus.

Figure 3. Antitumor effect of MV-CEA, administered intratumorally in an orthotopic U87 tumor model

Tumors were established by injection of 10⁶ U87 cells into the right caudate nucleus of BALB/c nude mice. Mice were randomly assigned to either MV-CEA treatment (1.8 × 10⁶ TCID₅₀), UV-inactivated MV-CEA treatment, or remained untreated. Significant prolongation of survival was observed in the mice treated with MV-CEA, as compared to mice that received UV-inactivated MV-CEA or no treatment (p = 0.02). Reproduced with permission from Phuong L, et al. Cancer Res 2003 [17]. CEA: Carcinoembryonic antigen; MV: Measles virus; TCID₅₀: Tissue culture infective dose.

Figure 4. Serum CEA plotted with U87 subcutaneous tumor volume in BALB/c nude mice treated with intravenous MV-CEA

The rise and fall of serum CEA parallel the growth and regression of the tumor. Reproduced with permission from Phuong L, et al. Cancer Res 2003 [17]. CEA: Carcinoembryonic antigen; MV: Measles virus.