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.
Highlights
Human epidermal growth factor-like receptor (HER2/neu) is an oncogene that belongs to the transmembrane receptor family with 100 folds higher expression in tumor cells than normal tissues [1]
The results indicated that GP2 peptide can induce a cytotoxic T lymphocyte (CTL) response similar to E75 and it is or more immunogenic [11]
The results demonstrated that IFN-γ was increased by 1.85 ±0.4 in splenocytes of mice immunized with Lip-DOPE-Monophosphoryl lipid A (MPL)-GP2 compared to the HEPS-dextrose 5% group 14 days after the last immunization, whereas IL-4 expression was found to be significantly decreased by 4.26819±1.5(Fig 5)
Summary
Human epidermal growth factor-like receptor (HER2/neu) is an oncogene that belongs to the transmembrane receptor family with 100 folds higher expression in tumor cells than normal tissues [1]. HER2/neu as an immunogenic protein elicits both humoral and cellular immune responses. This oncogene is an important biomarker and the goal of therapy for almost 30% of all breast cancers[2]. Immunotherapy is a treatment that uses certain parts of a person’s immune system to attack cancer cells [3]. Cancer vaccines belong to a class of substances known as biological response modifiers that work by stimulating or restoring the immune system’s ability to fight infections and disease. There are two broad types of cancer vaccines: prophylactic vaccines, which are intended to prevent cancer from developing in healthy people, and the second group, therapeutic vaccines, are intended to treat existing cancers by strengthening the body’s natural immune response [5]
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