Conjugated nanoliposome with the HER2/neu-derived peptide GP2 as an effective vaccine against breast cancer in mice xenograft model

Abstract

One of the challenging issues in vaccine development is peptide and adjuvant delivery into target cells. In this study, we developed a vaccine and therapeutic delivery system to increase cytotoxic T lymphocyte (CTL) response against a breast cancer model overexpressing HER2/neu.Gp2, a HER2/neu-derived peptide, was conjugated to Maleimide-mPEG2000-DSPE micelles and post inserted into liposomes composed of DMPC, DMPG phospholipids, and fusogenic lipid dioleoylphosphatidylethanolamine (DOPE) containing monophosphoryl lipid A (MPL) adjuvant (DMPC-DMPG-DOPE-MPL-Gp2). BALB/c mice were immunized with different formulations and the immune response was evaluated in vitro and in vivo. ELISpot and intracellular cytokine analysis by flow cytometry showed that the mice vaccinated with Lip-DOPE-MPL-GP2 incited the highest number of IFN-γ+ in CD8+ cells and CTL response. The immunization led to lower tumor sizes and longer survival time compared to the other groups of mice immunized and treated with the Lip-DOPE-MPL-GP2 formulation in both prophylactic and therapeutic experiments. These results showed that co-formulation of DOPE and MPL conjugated with GP2 peptide not only induces high antitumor immunity but also enhances therapeutic efficacy in TUBO mice model. Lip-DOPE-MPL-GP2 formulation could be a promising vaccine and a therapeutic delivery system against HER2 positive cancers and merits further investigation.

Nanoparticles to Improve the Efficacy of Peptide-Based Cancer Vaccines

“…Polymeric nanoparticles have been developed as antigen delivery system and, in particular, poly( D-L -lactic-co-glycolide) nanoparticles (PLGA-NPs) are the best known model used in cancer vaccine together with PEG ( Figure 2) [22,23].…”

“…Polymeric nanoparticles have been developed as antigen delivery system and, in particular, poly(D-L-lactic-co-glycolide) nanoparticles (PLGA-NPs) are the best known model used in cancer vaccine together with PEG ( Figure 2) [22,23]. Moreover, physicochemical properties (e.g., hydrophobicity, surface charge), drug release profile and biological behavior (e.g., bioadhesion, targeted drug delivery, improved cellular uptake) can be modulated by application of different polymeric materials and targeting ligands [24].…”

“…The efficacy of PLGA NPs and PLGA/PEI NPs (polyethylenimine) as peptide delivery system for therapeutic cancer vaccine development was assessed in an ex vivo cell culture model [23]. Flow cytometry as well as confocal laser scanning microscopy (CLSM) showed that PLGA/PEI NPs are more readily taken up by both human CD14 + monocytes and mouse Hepa 1-6 hepatoma cell line compared to PLGA NPs.…”

“…Such a differentiation was associated with a Th1 phenotype. The same OVA antigen in a soluble form was unable to induce maturation of DCs, indicating that both NP formulations provided an intrinsic adjuvant effect combined to efficient antigen delivery [23].…”

The Role of Self-Assembling Lipid Molecules in Vaccination

“…Peptides and proteins are the most common antigens used for vaccination. Preparations of peptides and liposomes have shown their efficacy many times and for multiple applications, including protection against a large variety of pathogens [69,70] and cancer [71]. Furthermore, peptides delivered via liposome formulations have and are been extensively used in many immunology studies as stimulants of the humoral response (e.g., Taenechi and colleges recently demonstrated that liposome-coupled peptides induce long-lived memory CD8 T cells without CD4 T cells using liposome-based vaccines [72]).…”