Table 4.

Preclinical studies using retargeted attenuated measles virus.

Target disease	Transgenic expressed proteins	Targeted receptor and cells	Administration route	Preclinical assay	Parental strain	Receptors used for viral entry	References
Multiple Myeloma	A disintegrin ML-28L echistatin (MV-ERV measles virus echistatin vector)	Integrin alpha(v)beta3 expressed on activated but not quiescent endothelial cells (targeting tumors and their associated blood vessels)	Intratumoral	mice	MV Edmonston B	CD150, CD46, integrin αvβ3	96
Breast cancer	Amino-terminal fragment of the urokinase plasminogen activator (uPA) (of human or mice) targeting uPAR (MV-uPA),	Urokinase receptor (uPAR) on activated endothelial cells (tumor vascular targeting)	IV	mice	Edmonston vaccine lineage NSe strain11.	uPAR, CD46, CD150	98
Non-Hodgkin's Lymphoma (NHL)	CD-20 targeted MV vector expressing the prodrug convertase purine nucleoside phosphorylase (PNP)	CD20 (B-cell specific antigen CD20)	Intracerebral administration	mice	Edmonston vaccine lineage NSe strain	CD20, (ablation of CD46 and CD150 interactions)	99
Glioblastoma multiforme (GBM)	Human IL-13, GFP	Interleukin-13-receptor α2 (IL-13R α2)	Intracerebral administration	mice	Edmonston vaccine lineage NSe strain	IL-13Rα2, (ablation of CD46 and CD150 interactions)	100
Glioblastoma multiforme	a single chain antibody recognizing EGFR, GFP	Epidermal growth factor receptor (EGFR) or EGFRvIII (the most common EGFR mutant) (EGFR is a glioma-specific receptor)	Intracerebral administration	mice	Edmonston vaccine lineage NSe strain	EGFR or EGFRvIII, (ablation of CD46 and CD150 interactions)	101
Myeloma	Oncolytic MV displaying αvβ3 integrin-binding peptides, cyclic arginine-glycine-aspartate (RGD) or echistatin (integrins)4 recombinant MV displaying cyclic RGD or echistatin and GFP	Both viruses had expanded tropisms, and efficiently entered target cells via binding to integrinsNeovessel endothelial cells in vivo	iv	mice	cDNAs of the virulent IC-B strain isolated in a lymphoid cell line, B95a2	CD46-CD150-EGFR	103
Ovarian cancer	MV-αFV: a single-chain antibody (scFv) specific for α-folate receptor	Folate receptor	Sc, ip	Mice	Edmonston vaccine lineage NSe strain	Folate receptor (ablation of CD46 and CD150 interactions)	104

¹The virus is derived from the Edmonston vaccine lineage NSe strain; it was rescued using the pseudoreceptor STAR (6 His tagging and retargeting) system propagated on Vero-HIS cells. The viral H protein contains the CD46-ablating mutation Y481A and the SLAM-ablatting mutation R533A. it also contains the GFP which facilitates viral rescue and allows visualization of infection in vitro and in vivo.⁹⁷

²The rescue system uses Chine hamster ovary cells expressing CD150 (CHO/hSLAM) and the recombinant vaccinia virus LO-T7-1 (the lister strain had been used as a vaccine in the WHO smallpox eradication programme).¹⁰²