ABSTRACT
Background: An increasing number of tumor associated antigens (TAA) capable of inducing immune responses have been identified in the last two decades. Unfortunately, they are weak immunogens and require potent adjuvants to promote their immunogenicity. Virosomes, nano-lipid vesicles containing viral protein spikes, have been proven amenable for transferring antigen (Ag) to the major histocompatibility complex (MHC) class I processing pathway with the aim to prime cytotoxic T-ymphocytes (CTL) responses. Objective: This mini-review outlines the virosomes platform, ranging from virosomal preparation, their intracellular trafficking and mechanism of action. Methods: The review is directed toward an application of virosomes as a novel and potential vaccine adjuvant in active cancer immunotherapy. Results and conclusion: Virosomes have been proven to be a suitable TAA delivery carrier. Ag encapsulated inside the lumen of virosomes could be prevented from serum- and cell-associated peptidases. Virosomes also facilitated the intracellular trafficking of encapsulated Ag, in which Ag could reach the cytosol and be presented by the MHC-Class I machinery. In addition, virosomes with TAA encapsulated are amenable to be a novel tumor immunotherapeutic strategy.
ABSTRACT
Background: Imiquimod (IMQ), a small-molecule immune response modifier of the imidazoquinoline family, has been shown to activate functional maturation of dendritic cells (DCs) through the Toll-like receptor (TLR)7- signaling pathway. IMQ has the potential to develop into a novel vaccine adjuvant. Currently, a topical cream of IMQ has been approved for the treatment of genital warts, superficial basal cell carcinoma and actinic keratosis. Objective: To develop nano-liposomes with encapsulated IMQ as a new vaccine adjuvant. Methods: Two types of nano-lipid particles containing IMQ which differed in their surface charge (i.e. positively and negatively charged liposomes) were prepared and characterized. Murine bone marrow derived DCs were cultured and treated with liposomal formulations. The surface marker expression of DCs was then determined by flow cytometry. Results: Both liposomes with IMQ encapsulated enhanced DCs maturation as determined by the surface marker expression of DCs (CD80, CD86, and MHC class II). Cationic liposomes induced high levels of surface marker expression of DCs in similar levels as those induced by lipopolysaccharides (LPS). Conclusion: The novel IMQ formulation, nano-liposome, has the benefits of simplicity and it enhances the adjuvant effect of IMQ.