Internalization, intracellular trafficking, and biodistribution of monoclonal antibody 806: a novel anti-epidermal growth factor receptor antibody. 2007

Rushika M Perera, and Roberto Zoncu, and Terrance G Johns, and Marc Pypaert, and Fook-Thean Lee, and Ira Mellman, and Lloyd J Old, and Derek K Toomre, and Andrew M Scott
Ludwig Institute for Cancer Research, Austin Hospital, Heidelberg, Victoria 3084, Australia.

Overexpression of the epidermal growth factor receptor (EGFR) in epithelial tumors is associated with poor prognosis and is the target for a number of cancer therapeutics. Monoclonal antibody (mAb) 806 is a novel anti-EGFR antibody with significant therapeutic efficacy in tumor models when used as a single agent, and displays synergistic antitumor activity in combination with other EGFR therapeutics. Unlike other EGFR antibodies, mAb 806 is selective for tumor cells and does not bind to normal tissue, making it an ideal candidate for generation of radioisotope or toxin conjugates. Ideally, antibodies suited to these therapeutic applications must bind to and actively internalize their cognate receptor. We investigated the intracellular trafficking of fluorescently tagged mAb 806 in live cells and analyzed its biodistribution in a tumor xenografted nude mouse model. Following binding to EGFR, mAb 806 was internalized through dynamin-dependent, clathrin-mediated endocytosis. Internalized mAb 806 localized to early endosomes and subsequently trafficked to and accumulation in lysosomal compartments. Furthermore, biodistribution analysis in nude mice showed specific uptake and retention of radiolabeled mAb 806 to human tumor xenografts. These results highlight the potential use of mAb 806 for generation of conjugates suitable for diagnostic and therapeutic use in patients with EGFR-positive malignancies.

UI MeSH Term Description Entries
D008247 Lysosomes A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes MEMBRANE FUSION. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). Autolysosome,Autolysosomes,Lysosome
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008819 Mice, Nude Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses. Athymic Mice,Mice, Athymic,Nude Mice,Mouse, Athymic,Mouse, Nude,Athymic Mouse,Nude Mouse
D009363 Neoplasm Proteins Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm. Proteins, Neoplasm
D011992 Endosomes Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface. Receptosomes,Endosome,Receptosome
D004705 Endocytosis Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis. Endocytoses
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D000918 Antibody Specificity The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site. Antibody Specificities,Specificities, Antibody,Specificity, Antibody

Related Publications

Rushika M Perera, and Roberto Zoncu, and Terrance G Johns, and Marc Pypaert, and Fook-Thean Lee, and Ira Mellman, and Lloyd J Old, and Derek K Toomre, and Andrew M Scott
July 2001, Cancer research,
Rushika M Perera, and Roberto Zoncu, and Terrance G Johns, and Marc Pypaert, and Fook-Thean Lee, and Ira Mellman, and Lloyd J Old, and Derek K Toomre, and Andrew M Scott
January 2024, Molecules (Basel, Switzerland),
Rushika M Perera, and Roberto Zoncu, and Terrance G Johns, and Marc Pypaert, and Fook-Thean Lee, and Ira Mellman, and Lloyd J Old, and Derek K Toomre, and Andrew M Scott
January 1998, Nuclear medicine and biology,
Rushika M Perera, and Roberto Zoncu, and Terrance G Johns, and Marc Pypaert, and Fook-Thean Lee, and Ira Mellman, and Lloyd J Old, and Derek K Toomre, and Andrew M Scott
November 2019, Cell reports,
Rushika M Perera, and Roberto Zoncu, and Terrance G Johns, and Marc Pypaert, and Fook-Thean Lee, and Ira Mellman, and Lloyd J Old, and Derek K Toomre, and Andrew M Scott
April 1985, The Journal of biological chemistry,
Rushika M Perera, and Roberto Zoncu, and Terrance G Johns, and Marc Pypaert, and Fook-Thean Lee, and Ira Mellman, and Lloyd J Old, and Derek K Toomre, and Andrew M Scott
August 2009, Cancer research,
Rushika M Perera, and Roberto Zoncu, and Terrance G Johns, and Marc Pypaert, and Fook-Thean Lee, and Ira Mellman, and Lloyd J Old, and Derek K Toomre, and Andrew M Scott
April 2004, Cellular & molecular immunology,
Rushika M Perera, and Roberto Zoncu, and Terrance G Johns, and Marc Pypaert, and Fook-Thean Lee, and Ira Mellman, and Lloyd J Old, and Derek K Toomre, and Andrew M Scott
March 2022, Proceedings of the National Academy of Sciences of the United States of America,
Rushika M Perera, and Roberto Zoncu, and Terrance G Johns, and Marc Pypaert, and Fook-Thean Lee, and Ira Mellman, and Lloyd J Old, and Derek K Toomre, and Andrew M Scott
January 1989, Biochemical and biophysical research communications,
Rushika M Perera, and Roberto Zoncu, and Terrance G Johns, and Marc Pypaert, and Fook-Thean Lee, and Ira Mellman, and Lloyd J Old, and Derek K Toomre, and Andrew M Scott
October 2002, Neurosurgery,
Copied contents to your clipboard!