PuSH - Publikationsserver des Helmholtz Zentrums München: EBV-gp350 confers B-cell tropism to tailored exosomes and is a neo-antigen in normal and malignant B cells

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Ruiss, R. ; Jochum, S. ; Mocikat, R. ; Hammerschmidt, W. ; Zeidler, R.*

EBV-gp350 confers B-cell tropism to tailored exosomes and is a neo-antigen in normal and malignant B cells - a new option for the treatment of B-CLL.

PLoS ONE 6:e25294 (2011)

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gp350, the major envelope protein of Epstein-Barr-Virus, confers B-cell tropism to the virus by interacting with the B lineage marker CD21. Here we utilize gp350 to generate tailored exosomes with an identical tropism. These exosomes can be used for the targeted co-transfer of functional proteins to normal and malignant human B cells. We demonstrate here the co-transfer of functional CD154 protein on tailored gp350+ exosomes to malignant B blasts from patients with B chronic lymphocytic leukemia (B-CLL), rendering B blasts immunogenic to tumor-reactive autologous T cells. Intriguingly, engulfment of gp350+ exosomes by B-CLL cells and presentation of gp350-derived peptides also re-stimulated EBV-specific T cells and redirected the strong antiviral cellular immune response in patients to leukemic B cells. In essence, we show that gp350 alone confers B-cell tropism to exosomes and that these exosomes can be further engineered to simultaneously trigger virus- and tumor-specific immune responses. The simultaneous exploitation of gp350 as a tropism molecule for tailored exosomes and as a neo-antigen in malignant B cells provides a novel attractive strategy for immunotherapy of B-CLL and other B-cell malignancies.

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