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

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-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.

• Authors: R Chignola, M Pasti, C Candiani, A Franceschi, C Anselmi, G Tridente, M Colombatti
• Journal: International journal of cancer (Int J Cancer) Vol. 61 Issue 4 Pg. 535-41 (May 16 1995) ISSN: 0020-7136 [Print] United States
• PMID: 7538979 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antigens, CD
• CD5 Antigens
• Immunotoxins
• Ricin

Topics

• Antibodies, Monoclonal (pharmacokinetics, therapeutic use)
• Antigens, CD (immunology)
• CD5 Antigens
• Cell Death (drug effects)
• Cell Division (drug effects)
• Drug Resistance (physiology)
• Evaluation Studies as Topic
• Humans
• Immunotoxins (pharmacokinetics, therapeutic use)
• Leukemia, Lymphoid (drug therapy, metabolism)
• Ricin (pharmacokinetics, therapeutic use)
• Tumor Cells, Cultured