title: 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.
abstract: 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.
authors.affiliation: Laboratory of Cytometry, Centre of Postgraduate Medical Education, Warsaw, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Gryzik
authors.affiliation: Laboratory of Cytometry, Centre of Postgraduate Medical Education, Warsaw, Poland.
authors.forename: Z
authors.initials: Z
authors.lastname: Grzywocz
authors.affiliation: Laboratory of Cytometry, Centre of Postgraduate Medical Education, Warsaw, Poland.
authors.forename: D
authors.initials: D
authors.lastname: Wasilewska
authors.affiliation: Laboratory of Cytometry, Centre of Postgraduate Medical Education, Warsaw, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Kawiak
authors.affiliation: Department of Applied Microbiology, Institute of Microbiology, Faculty of Biology, Warsaw University, Warsaw, Poland.
authors.forename: R
authors.initials: R
authors.lastname: Stachowiak
authors.affiliation: Department of Applied Microbiology, Institute of Microbiology, Faculty of Biology, Warsaw University, Warsaw, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Bielecki
authors.affiliation: Laboratory of Cytometry, Centre of Postgraduate Medical Education, Warsaw, Poland Department of Clinical Cytology, Centre of Postgraduate Medical Education, Warsaw, Poland ghoser@cmkp.edu.pl.
authors.forename: G
authors.initials: G
authors.lastname: Hoser
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018951:Antigens, CD20 / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects*; D001427:Bacterial Toxins / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003165:Complement System Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000494:pharmacology*; D006460:Hemolysin Proteins / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D000069283:Rituximab / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D007166:Immunosuppressive Agents; D000069283:Rituximab; D003165:Complement System Proteins; C038705:hlyA protein, Listeria monocytogenes
keywords: cytotoxicity; flow cytometry; human plasma; leukemia; listeriolysin O; rituximab