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

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

BH3-only protein Bmf mediates apoptosis upon inhibition of CAP-dependent protein synthesis

International audienc

Immune reconstitution in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is associated with a profound immune defect, which results in increased susceptibility to recurrent infections as well as a failure to mount effective antitumor immune responses. Current chemotherapy-based regimens are not curative and often worsen this immune suppression, so their usefulness is limited, particularly in the frail and elderly. This article reviews the immune defect in CLL and discusses strategies aimed at repairing or circumventing this defect. In particular, it focuses on recent developments in the areas of CD40 ligand (CD40L/CD154) gene therapy, immunomodulatory agents such as lenalidomide, and adoptive transfer of T cells bearing chimeric antigen receptors