Preparation of nanoliposomes linked to her2/neu-derived antigens as vaccine against breast cancer and evaluation of anti-tumor effects and immunologicalresponses

Nanoliposomes have been widely found to be effective as both adjuvant and delivery system for vaccine development. HER-2/ neu is an immunogenic protein eliciting both humoral and cellular immune responses in patients with HER-2/ neu-positive tumors. The goal of the study was to induce and enhance an effective cytotoxic T lymphocyte (CTL) response against peptide P5+P435 derived from rat HER-2/neu oncogene by employing the potential benefit of liposomes as a delivery vehicle. The antigen-specific CTLs are major effector cells in tumor immunity. MPL has been also shown to exert a potent adjuvant activity for a wide range of antigens. In this study, the P435+P5 peptide was conjugated to DSPE- mPEG2000- Maleimide lipid and coupled on the surface of nanoliposomes containing MPL. Different groups of mice were subcutaneously vaccinated with four formulations containing 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC)/ 1,2-Distearoyl-sn-glycero-3- phosphoglycerol (DSPG)/Cholesterol (15:2:3) with or without dioleoyl phosphatidy lethanolamine (DOPE), MPL (25 μg per mouse), and the peptide conjugated to DSPE- mPEG2000- Maleimide lipid (10 μg per mouse). Three vaccine administrations were carried out at 2-week intervals. Two weeks after last boosting, splenocytes were harvested from vaccinated and control mice for immunoassay. Released amount of IFN-γ was determined by ELISpot kits and flow cytometric analysis was used to identify IFN-γ and IL-4 producing cells. Tumor size and survival time were monitored in mice for a period of 110 days. Mice immunized with Liposome-DOPE-P5+435 formulation showed the most released IFN- γ and the highest CTL responses. Consequently, these responses led to lower tumor sizes and longer survival time in TUBO tumor mice model. This study showed that linked forms of rHER2/neu- peptides (P5+P435) can induce an antigen-specific CTL immunity in TUBO tumor mice model

کلیدواژه ها:

Breast Cancer ، Solid Tumors ، Cancer Treatment and Management ، Targeted Cancer Therapy ، Drugs and Cancer