Antibody-targeted cell fusion

Membrane fusion has many potential applications in biotechnology. Here we show that antibody-targeted cell fusion can be achieved by engineering a fusogenic viral membrane glycoprotein complex. Three different single-chain antibodies were displayed at the extracellular C terminus of the measles hema...

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Bibliographic Details
Published in:Nature biotechnology 2004-03, Vol.22 (3), p.331-336
Main Authors: Russell, Stephen J, Nakamura, Takafumi, Peng, Kah-Whye, Vongpunsawad, Sompong, Harvey, Mary, Mizuguchi, Hiroyuki, Hayakawa, Takao, Cattaneo, Roberto
Format: Article
Language:English
Subjects:
Agriculture
Animals
Antigen-Antibody Complex - genetics
Antigen-Antibody Complex - immunology
Antigens, CD - genetics
Antigens, CD - immunology
Bioinformatics
Biological and medical sciences
Biomedical and Life Sciences
Biomedical Engineering/Biotechnology
Biomedicine
Biotechnology
CD46 antigen
Cell Line, Tumor
Cell Membrane - genetics
Cell Membrane - immunology
Cell Membrane - pathology
Cells, Cultured
Cercopithecus aethiops
Drug Delivery Systems - methods
Female
Fundamental and applied biological sciences. Psychology
Glycoproteins - genetics
Glycoproteins - immunology
Health. Pharmaceutical industry
Humans
Immunoglobulins - genetics
Immunoglobulins - immunology
Industrial applications and implications. Economical aspects
letter
Life Sciences
Measles virus
Membrane Cofactor Protein
Membrane Fusion - genetics
Membrane Fusion - immunology
Membrane Glycoproteins - genetics
Membrane Glycoproteins - immunology
Membranes
Mice
Mice, Nude
Miscellaneous
Mutation
Neoplasms - genetics
Neoplasms - immunology
Neoplasms - pathology
Neoplasms - therapy
Protein Engineering - methods
Proteins
Receptors, Cell Surface
Recombinant Proteins - immunology
Signaling Lymphocytic Activation Molecule Family Member 1
Treatment Outcome
Tumors
Vero Cells
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Description
Summary:Membrane fusion has many potential applications in biotechnology. Here we show that antibody-targeted cell fusion can be achieved by engineering a fusogenic viral membrane glycoprotein complex. Three different single-chain antibodies were displayed at the extracellular C terminus of the measles hemagglutinin (H) protein, and combinations of point mutations were introduced to ablate its ability to trigger fusion through the native viral receptors CD46 and SLAM. When coexpressed with the measles fusion (F) protein, using plasmid cotransfection or bicistronic adenoviral vectors, the retargeted H proteins could mediate antibody-targeted cell fusion of receptor-negative or receptor-positive index cells with receptor-positive target cells. Adenoviral expression vectors mediating human epidermal growth factor receptor (EGFR)-targeted cell fusion were potently cytotoxic against EGFR-positive tumor cell lines and showed superior antitumor potency against EGFR-positive tumor xenografts as compared with control adenoviruses expressing native (untargeted) or CD38-targeted H proteins.
ISSN:1087-0156
1546-1696
DOI:10.1038/nbt942