Virosome-mediated delivery of tumor antigen to plasmacytoid dendritic cells

Abstract

Cytotoxic T lymphocytes (CTL) are crucial in viral clearance and tumor growth control. Thus the induction of CTL activity is an important aim in vaccine development. We investigate an innovative delivery system for peptide transfer to the MHC class-I processing pathway of APC with the aim to trigger CTL in the context of an anti-tumoral response. The strategy relies on a novel antigen delivery system termed "chimeric immunopotentiating reconstituted influenza virosomes" (CIRIV) targeting plasmacytoid dendritic cells (PDC). By using virosomes containing encapsulated Melan-A peptide and a PDC line developed in our laboratory, we evaluated the response of Melan-A specific T cells. Virosomes have the capacity to bind PDC and are endocyted within vesicles in the cytosol. This endocytosis is inhibited by neuraminidase, suggesting that it is mediated by sialic acid present on cell surface. Furthermore, PDC loaded with Melan-A virosomes can induce a Melan-A specific T cell activation. Interestingly, they activate T cells with a better efficiency than PDC loaded with a free peptide and when PDC where previously activated by a TLR ligand. These results indicate that virosomes could be a suitable delivery system for tumor peptide in immunotherapy of cancer.

Targeted Delivery of Protein Drugs by Nanocarriers

“…Clearly, to use this kind of nanocarrier for drug delivery, the viral genetic information must be removed from the virus shell in order to avoid infection of the cell. The emptied viral shell (virosome) can be used to deliver molecules (e.g., DNA [81], RNA [82], antigens [83], vaccines [84,85]) directly into cells, especially in gene therapy (Figure 2). Virosomes are often obtained from influenza virus by solubilization of the viral membrane followed by ultracentrifugation and reconstitution of the envelope by elimination of the detergent [86].…”

Intracellular Bacterial Vectors That Induce CD8+ T Cells with Similar Cytolytic Abilities but Disparate Memory Phenotypes Provide Contrasting Tumor Protection

“…Despite the success in generating CD8 + T-cell responses to self antigens (1)(2)(3)(4)(5)(6), cancer immunotherapy has provided objective long-term remission in only a small proportion of patients with select cancer types (7). Moreover, cancer resurgence occurs despite the presence of tumor-specific CD8 + T cells (8).…”

Virosome Presents Multimodel Cancer Therapy without Viral Replication

“…Therefore, it is suggested that influenza virosomes introduce encapsulated TAAs to the cytoplasm through membrane fusion and that TAA introduction is needed for the presentation of TAAs on MHC-I. Angel et al reported influenza virosome-mediated delivery of TAAs to DCs [60]. The authors encapsulated the Melan-A peptide, which is a TAA from melanoma, in an influenza virosome and introduced the Melan-A peptide into plasmacytoid DCs (PDCs).…”