CD154 is a known promising candidate molecule for the immunotherapy of B-CLL because it increases the immunogenicity of the tumor cells. In line, the ectopic expression of CD154 on B-CLL cells was shown to induce the expression of important costimulatory and adhesion molecules on the leukemic cells, turning them into efficient stimulators of autologous T cells. In principle, viral gene transfer of CD154 into B-CLL cells is a suitable approach to induce immunological reactions both in vitro and in vivo [14, [26] [27] [28] [29] but the low transduction efficiency and the resulting high dose of viral vectors may induce severe side effects. There also remain major concerns about the clinical use of viral vectors.