Human lymphocytic B-leukemia cell line treatment with the bacterial toxin listeriolysin O and rituximab (anti-CD20 antibody): Effects of similar localization of their receptors

Small B-cell lymphocytic lymphoma/chronic lymphocytic leukemia, which typically affects elderly people, is a group of conditions that are not clinically uniform. It has been suggested that using the combined activity of the monoclonal antibody anti-CD20 (rituximab) and Listeria monocytogenes toxin l...

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Bibliographic Details
Published in:	International journal of immunopathology and pharmacology Vol. 28; no. 3; p. 329
Main Authors:	Gryzik, M, Grzywocz, Z, Wasilewska, D, Kawiak, J, Stachowiak, R, Bielecki, J, Hoser, G
Format:	Journal Article
Language:	English
Published:	England 01-09-2015
Subjects:	Antibodies, Monoclonal - pharmacology Antigens, CD20 - metabolism B-Lymphocytes - drug effects Bacterial Toxins - pharmacology Cell Line, Tumor Complement System Proteins - metabolism Heat-Shock Proteins - pharmacology Hemolysin Proteins - pharmacology Humans Immunosuppressive Agents - pharmacology Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy Rituximab - pharmacology leukemia flow cytometry cytotoxicity human plasma listeriolysin O rituximab
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Summary:	Small B-cell lymphocytic lymphoma/chronic lymphocytic leukemia, which typically affects elderly people, is a group of conditions that are not clinically uniform. It has been suggested that using the combined activity of the monoclonal antibody anti-CD20 (rituximab) and Listeria monocytogenes toxin listeriolysin O (LLO) for this condition could produce an enhanced treatment effect. Here, we tested the effect of the joint activity of rituximab and LLO, which is a cell membrane toxin, in human leukemia cell lines. The human B-leukemia Raji cell line, which expresses CD20, and the T-cell Jurkat cell line, which does not express CD20, for comparison were used in model tests. Cell cytotoxicity of rituximab or LLO and both applied jointly to the cell lines was compared in the presence of human plasma complement. Optimal cytotoxic effects dependent on rituximab or LLO concentration were tested separately. LD50 values were determined and used for optimal application of a mixture of the two factors. The cytotoxic effect on Raji cells of both rituximab and LLO was more than 2.5 times that of LLO alone and 1.5 times that of rituximab alone. At the highest tested concentrations, a mixture of the tested factors had a non-specific cytotoxic effect on the Jurkat cell line, as well. The rituximab and LLO binding sites appear to be in a similar region of the Raji leukemia cell membrane, suggesting an effective interaction of both factors. The joint interaction of these compounds in cell membrane pore formation suggests an explanation for the more effective cytotoxic activity that their combination was observed in this experiment.
ISSN:	0394-6320
DOI:	10.1177/0394632015595778