Escape mechanisms of human leukemic cells to long-term immunotoxin treatment in an in vitro experimental model
✍ Scribed by Roberto Chignola; Marcella Pasti; Carola Candiani; Antonia Franceschi; Cristina Anselmi; Giuseppe Tridente; Marco Colombatti
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- French
- Weight
- 830 KB
- Volume
- 61
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
In kinetic assays, an anti‐CD5‐ricin A chain (ST.1 ‐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‐RTA treatment on Jurkat cells was only to delay cell growth for a limited time period (20 hr) without reducing effectively the tumor‐cell burden. Our results may have implications for the long‐term treatment of target tumor cells with IT. © 1995 Wiley‐Liss, Inc.