Internalization and action of an immunotoxin containing mistletoe lectin A-chain.
An immunotoxin consisting of the enzymatically active A-chain of mistletoe lectin I and a monoclonal antibody against a surface protein on mouse leukemia L1210V cells was found to inhibit protein synthesis in these cells as efficiently as the native mistletoe toxin. The immunotoxin was somewhat more slowly endocytosed than the native toxin, but in both cases the endocytic uptake continued under conditions in which uptake from clathrin-coated pits was inhibited by mild acidification of the cytosol. This indicates that the toxin and the immunotoxin were at least partially internalized by a non-clathrin-dependent uptake mechanism and that uptake by this pathway is responsible for most of the toxic effect on the cells. The results indicate that efficient immunotoxins can be made with antibodies against cell surface epitopes that are endocytosed by a mechanism not involving clathrin-coated pits.
Wiedłocha
A
A
Institute for Cancer Research, Norwegian Radium Hospital, Montebello, Oslo, Norway.
Sandvig
K
K
Walzel
H
H
Radzikowsky
C
C
Olsnes
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D003600:Cytosol; D004705:Endocytosis; D006863:Hydrogen-Ion Concentration; D000922:Immunotoxins / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D037102:Lectins / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D014784:Mistletoe; D037121:Plant Lectins; D028321:Plant Preparations; D010940:Plant Proteins; D010946:Plants, Medicinal; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D037102:Lectins; D037121:Plant Lectins; D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C009674:ribosome inactivating protein, Viscum