Intracellular delivery of monoclonal antibodies

With some exceptions, antibodies do not have the ability to penetrate cell membranes and act intracellularly. Their usefulness in research and medicine would be considerably enhanced if they had the intrinsic ability to act on intracellular targets. We report here that covalently linking poly- l-arg...

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Bibliographic Details
Published in:Immunology letters 2002-10, Vol.84 (1), p.63-67
Main Authors: Chen, Bi-Xing, Erlanger, Bernard F
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Antibodies, Monoclonal - administration & dosage
Antibodies, Monoclonal - chemistry
Antibodies, Monoclonal - pharmacokinetics
Biological Transport, Active
Cell Line
Gene Products, gag
HeLa Cells
HIV Antibodies - administration & dosage
HIV Antibodies - chemistry
HIV Antibodies - metabolism
HIV-1 - immunology
Humans
Hybridomas
Immunoglobulins
Intracellular Fluid - immunology
Mice
Peptides - administration & dosage
Peptides - chemistry
Peptides - pharmacokinetics
Polyarginine
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Summary:With some exceptions, antibodies do not have the ability to penetrate cell membranes and act intracellularly. Their usefulness in research and medicine would be considerably enhanced if they had the intrinsic ability to act on intracellular targets. We report here that covalently linking poly- l-arginine (average molecular weight 10,750, ca. 68 residues) to the oligosaccharide moiety of the CH2 region of an immunoglobulin makes possible penetration into the cytoplasm and, and in some cases into the nucleus of cells. We demonstrate this with five antibodies and seven cell lines. Retention of specificity is demonstrated by ELISA with an anti-HIV Gag antibody and intracellularly with a monoclonal anti-tubulin antibody. As the antibodies are covalently modified, they have the potential to be used in intact animals.
ISSN:0165-2478
1879-0542
DOI:10.1016/S0165-2478(02)00146-3