This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wiedlocha, A. Articles by Olsnes, S. Search for Related Content PubMed PubMed Citation Articles by Wiedlocha, A. Articles by Olsnes, S.

Internalization and Action of an Immunotoxin Containing Mistletoe Lectin A-Chain¹

Antoni Widocha, Kirsten Sandvig, Hermann Walzel, Czeslaw Radzikowsky and Sjur Olsnes²

Institute for Cancer Research at The Norwegian Radium Hospital, Montebello, 0310 Oslo 3, Norway [A. W., K. S., S. O.]; Institute of Biochemistry, Rostock University, Rostock, Germany [H. W.]; and Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Czerska 12, Wroclaw, Poland [A. W., C. R.]

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.

¹ This work was supported by The Norwegian Research Council for Science and Humanities, by The Norwegian Cancer Society, by Rakel og Kr. Bruuns Legat, and by Torsteds Legat.

² To whom requests for reprints should be addressed.

Received 9/ 4/90. Accepted 11/15/90.

This article has been cited by other articles:

				T. Hajto, K. Hostanska, T. Berki, L. Palinkas, F. Boldizsar, and P. Nemeth Oncopharmacological Perspectives of a Plant Lectin (Viscum album Agglutinin-I): Overview of Recent Results from In vitro Experiments and In vivo Animal Models, and Their Possible Relevance for Clinical Applications Evid. Based Complement. Altern. Med., March 1, 2005; 2(1): 59 - 67. [Full Text] [PDF]