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-cllebv-gp350授予定制液和b细胞趋向性是neo-antigen在正常和恶性b治疗b-cll电路新选项.pdfVIP

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 1 1 2 1 3 Romana Ruiss , Simon Jochum , Ralph Mocikat , Wolfgang Hammerschmidt , Reinhard Zeidler * ¨ 1 Department of Gene Vectors, Helmholtz-Zentrum, Munich, Germany, 2 Institut fur Molekulare Immunologie, Helmholtz-Zentrum, Munich, Germany, 3 Department of ¨ Otorhinolaryngology, Ludwig-Maximilians-Universitat, Munich, Germany Abstract 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 mo