Engineering extracellular vesicles as novel treatment options: exploiting herpesviral immunity in CLL

ABSTRACT

Extracellular vesicles (EVs) are important mediators of cell–cell communication. Intriguingly, EVs can be engineered and thus exploited for the targeted transfer of functional proteins of interest. Thus, engineered EVs may constitute attractive tools for the development of novel therapeutic interventions, like cancer immunotherapies, vaccinations or targeted drug delivery. Here, we describe a novel experimental immunotherapeutic approach for the adjuvant treatment of chronic lymphocytic leukaemia (CLL) based on engineered EVs carrying gp350, the major glycoprotein of Epstein–Barr virus (EBV), CD40L, a central immune accessory molecule and pp65, an immunodominant antigen of the human cytomegalovirus (CMV). We show that these engineered EVs specifically interact with malignant B cells from CLL patients and render these cells immunogenic to allogeneic and autologous EBV- and CMV-specific CD4+ and CD8+ T cells. Collectively, co-opting engineered EVs to re-target the strong herpesviral immunity in CLL patients to malignant cells constitutes an attractive strategy for the adjuvant treatment of a still incurable disease.

Abbreviations: CLL: chronic lymphocytic leukaemia; EBV: Epstein-Barr virus; CMV: cytomegalovirus

KEYWORDS:

• Extracellular vesicles
• immunotherapy
• CLL
• EBV
• CMV

Acknowledgements

We are indebted to all CLL patients for blood donation. We thank Josef Mautner and Andreas Moosmann, Research Unit Gene Vectors, Helmholtz Centre Munich, for the preparation of gp350- and pp65-specific T-cell clones and helpful discussions.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Marga und Walter Boll-Stiftung [210-05-13] and by institutional grants.