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Selective gene transfer to tumor cells by recombinant Newcastle Disease Virus via a bispecific fusion protein
Selective gene transfer to tumor cells by recombinant Newcastle Disease Virus via a bispecific fusion protein
- Source :
- International Journal of Oncology 26 (2005) 2, International Journal of Oncology, 26(2), 431-439
- Publication Year :
- 2005
-
Abstract
- Much interest exists presently in development of vectors for gene therapy of tumors based on RNA viruses because these viruses replicate in the cytoplasm and do not integrate into DNA. The negative stranded paramyxovirus, Newcastle Disease Virus (NDV) from chicken has the additional advantages of preferential replication in tumor cells and of oncolytic and immunostimulatory properties. We here describe the bispecific fusion protein alphaHN-IL-2 which binds to NDV, inhibits its normal cell binding property and introduces a new binding specificity for the interleukin-2 receptor (IL-2R). We demonstrate selective gene transfer to tumor cells expressing IL-2R via the bispecific fusion protein when using recombinant NDV carrying as marker gene the enhanced green fluorescence protein (NDFL-EGFP). Hemadsorption (HA) and neuraminidase activities (NA) of the HN protein of NDV were shown to be blocked by alphaHN-IL-2 simultaneously and the absence of HA-activity of modified NDV was confirmed in vivo. Retargeted virus-binding to IL-2R positive tumor cells was not sufficient for the process of cellular infection. It required in addition membrane fusion via the viral F-protein. By modification of recombinant NDV with a bispecific molecule, our results demonstrate a novel and safe strategy for selective gene transfer to targeted tumor cells.
- Subjects :
- Cancer Research
Time Factors
Genetic enhancement
viruses
Cell Separation
Recombinant virus
law.invention
Jurkat Cells
Mice
law
Neoplasms
Antibodies, Bispecific
Transgenes
Regulation of gene expression
Genetic transfer
Gene Transfer Techniques
Flow Cytometry
Up-Regulation
Oncology
Mice, Inbred DBA
Recombinant DNA
hemagglutinin-neuraminidase protein
phase-i
ID - Infectieziekten
animal structures
sialic-acid
Ultraviolet Rays
Recombinant Fusion Proteins
Genetic Vectors
Green Fluorescent Proteins
Newcastle disease virus
Neuraminidase
mechanism
Biology
disaggregation shear-stress
Animals
Humans
Hemadsorption
HN Protein
oncolytic virus
Dose-Response Relationship, Drug
Fusion protein
Molecular biology
infection
Oncolytic virus
Kinetics
single-chain antibody
Gene Expression Regulation
Interleukin-2
erythrocyte aggregation
Viral Fusion Proteins
rna viruses
Subjects
Details
- Language :
- English
- ISSN :
- 10196439
- Database :
- OpenAIRE
- Journal :
- International Journal of Oncology 26 (2005) 2, International Journal of Oncology, 26(2), 431-439
- Accession number :
- edsair.doi.dedup.....5f93f9cad7eec7997c2b6e4cd998a893