Oligonucleotide IMT504 induces an immunogenic phenotype and apoptosis in chronic lymphocytic leukemia cells

• Autores: Rodrigues, J.M.; Elias, F.; Montaner, A.; Flo, J.; Lopez, R.A.; Zorzopulos, J.; Franco, R.J.; Lenial, S.P.; Lopez Salón, M.; Pirpignani, M.L.; Solimano, J.; Garay, G.; Riveros, D.; Fernandez, J.; Cacchione, R.; Dupont, J.
• Año de publicación: 2006
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Medicina (Argentina) 2006;66(1):9-16
• Materia: Chronic lymphocytic leukemia; IL-2; Immunogenic phenotype; Immunostimulatory ODN; VH genes mutation; B7 antigen; CD40 antigen; CD86 antigen; immunoglobulin; interleukin 2 receptor alpha; oligodeoxynucleotide; recombinant interleukin 2; adult; aged; apoptosis; article; B lymphocyte activation; cancer growth; chronic lymphatic leukemia; clinical article; controlled study; dendritic cell; disease marker; female; gene mutation; human; human cell; immune system; immunogenicity; in vitro study; incubation time; leukemia cell; male; mixed lymphocyte reaction; phenotype; primate; protein expression; T lymphocyte activation; upregulation; Aged; Antigens, CD; Apoptosis; Female; Humans; Immunophenotyping; Interleukin-2; Leukemia, B-Cell, Chronic; Male; Middle Aged; Mutation; Oligodeoxyribonucleotides; Phenotype; Polymerase Chain Reaction
• Institución: Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales

Oligonucleotides (ODNs) of the PyNTTTTGT class directly stimulate B lymphocytes and plasmacytoid dendritic cells of the immune system of primates. Here we investigated the ability of the PyNTTTTGT ODN prototype IMT504 to regulate the expression of surface molecules and apoptosis in human B-chronic lymphocytic leukemia (CLL) cells. The surface molecules CD25, CD40, CD80 and CD86 were up-regulated upon incubation of the B-CLL cells with IMT504. Co-stimulation with IL-2 resulted in further up-regulation. IMT504-activated B-CLL cells were also good stimulators of T cells in allogeneic mixed lymphocyte reactions and co-stimulation with IL-2 improved this stimulation capacity. Apoptosis of the B-CLL cells in vitro was also stimulated by incubation with IMT504. In this case, co-stimulation with IL-2 was not significant. Furthermore, B-CLL cells of all the patients studied developed an immunogenic phenotype and entered stimulated apoptosis upon in vitro incubation with IMT504 independently of the mutational status of their 1gVH genes, becoming a good marker for tumor progression.
Fil:Elias, F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.