Treatment of B-CLL cells with exosomes transferring functional CD154 protein causes leukemia cells to become efficient APCs. Activating the CD40 receptor leads to the induction of immune accessory molecules, making these leukemic cells potent stimulators of autologous T lymphocytes. Since almost all patients with CLL have a high prevalence of EBV (94%) [31] and thus possess EBV-specific memory cells with a high frequency of CD4+ gp350specific T cells [32] , the incorporation of gp350 into exosomes has a dual function: it confers B-cell tropism and serves as an immunodominant viral CD4 antigen. The incorporation of a viral protein as a tumor-specific antigen is straightforward, because the cellular immune system of cancer patients is usually impaired but virus-specific immune responses are detectable even in late-stage patients and T lymphocytes specific for herpes viruses are often present at high numbers [1, 33] . Given the fact that the vast majority of CLL patients are seropositive for EBV, gp350 and other EBV proteins have the potential as promising neo-antigens in B-CLL cells exploiting and redirecting the strong anti-viral cellular immune responses to leukemic cells.