Immunostimulatory PyNTTTTGT Oligonucleotide IMT504 Induce an Immunogenic Phenotype and Apoptosis in Chronic Lymphocytic Leukemia Cells: Synergy with IL2 and Independency of the Mutational Status of the Ig VH Genes

RODRÍGUEZ JM, ELÍAS F, LÓPEZ SALÓN M, MONTANER A, FRANCO RJ, GENIAL SP, PIRPIGNANI M, FLÓ J, LÓPEZ RA AND ZORZOPULOS J

San Diego, CA. USA

Congreso; Experimental Biology. XXXV International Congress of Physiological Sciences; 2005

American Association of Immunologist

ODNs of the PyNTTTTGT class directly stimulate B and plasmacytoid dendritic cells of the immune system of primates (J. Immunol., 2003, 171: 3697-3704). Here we investigated the ability of the PyNTTTTGT ODN prototype IMT504 to regulate the expression of surface molecules in human B-Chronic Lymphocytic Leukemia (B-CLL) cells and the in vitro apoptosis behavior. The surface molecules CD25, CD40, CD80 and CD86 were up-regulated upon incubation of the B-CLL cells with IMT504. Co-stimulation with IL2 resulted in further up-regulation. IMT504-activated B-CLL cells were good stimulators of T cells in allogeneic mixed lymphocyte reactions and costimulation with IL2 improved the antigenic capacity. Furthermore, B-CLL cells of all the patients studied develop an immunogenic phenotype upon in vitro incubation with IMT504 independently of the mutational status of their IgVH genes. On the other hand, although immunostimulant ODNs are  known to rescue normal B cells from apoptosis; stimulated B-CLL cells with IMT504 increase the well known propensity of this tumor cells to enter in apoptosis under in vitro cultures.