PMID: 7538979May 16, 1995Paper

Escape mechanisms of human leukemic cells to long-term immunotoxin treatment in an in vitro experimental model

International Journal of Cancer. Journal International Du Cancer
R ChignolaM Colombatti

Abstract

In kinetic assays, an anti-CD5-ricin A chain (ST.I-RTA) immunoconjugate (immunotoxins, IT) specifically inhibited up to 40% the protein synthesis of Jurkat target cells within the first 40 hr. Longer exposures of leukemia cells to ST.I-RTA resulted in a progressively higher number of target cells escaping IT treatment and becoming resistant to further treatment with ST.I-RTA even in the presence of the RTA-IT enhancer monensin. Resistant Jurkat cells proliferated at the same rate as control untreated cells, and were as sensitive as control cells to a transferrin-RTA IT, indicating that the ST.I-RTA-resistant tumor-cell population did not become insensitive to the enzymatic activity of RTA. Binding studies revealed that the anti-CD5 IT treatment induced a transient modulation of CD5 antigens but not of the functionally related CD3 antigens. The CD5 antigens were re-expressed at the cell surface following removal of the IT molecules from the culture medium with 1.1% of the total CD5 Ag being re-expressed per hr. When our experimental data on the kinetics of cell intoxication by the IT were corrected for the proliferative potential of the resistant and of the sensitive tumor-cell populations, it appeared that the effect of ST.I-RT...Continue Reading

References

Dec 15, 1990·International Journal of Cancer. Journal International Du Cancer·R ChignolaG Tridente
May 7, 1990·Biochimica Et Biophysica Acta·H H MollenhauerL D Rowe
Nov 1, 1990·Clinical and Experimental Immunology·E J Wawrzynczak, A J Davies
Feb 15, 1989·International Journal of Cancer. Journal International Du Cancer·A A HertlerA E Frankel
Oct 1, 1986·Cellular Immunology·O W PressP J Martin
Jun 1, 1993·Immunology Today·E S VitettaJ W Uhr

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Citations

Sep 27, 1996·International Journal of Cancer. Journal International Du Cancer·M A GhetieE S Vitetta
Oct 3, 1999·International Journal of Cancer. Journal International Du Cancer·J PostG C De Gast
Dec 30, 1998·Leukemia & Lymphoma·B K Link, G J Weiner
Mar 29, 2011·Leukemia & Lymphoma·Michael Rosenblum, Peter McLaughlin

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