Preparation of nanoliposomes containing HER2/neu (P5+435) peptide and evaluation of their immune responses and anti-tumoral effects as a prophylactic vaccine against breast cancer

Abstract

HER2/neu is an immunogenic protein inducing both humoral and cell-mediated immune responses. The antigen-specific cytotoxic T lymphocytes (CTLs) are the main effector immune cells in the anti-tumor immunity. To induce an effective CTL specific response against P5+435 single peptide derived from rat HER2/neu oncogene, we used a liposome delivery vehicle. In vivo enhancement of liposome stability and intracytoplasmic delivery of peptides are the main strategies which elevate the liposome-mediated drug delivery. Liposomes containing high transition temperature phospholipids, such as DSPC, are stable with prolonged in vivo circulation and more accessibility to the immune system. Incorporation of DOPE phospholipid results in the effective delivery of peptide into the cytoplasm via the endocytotic pathway. To this end, the P5+435 peptide was linked to Maleimide-PEG2000-DSPE and coupled on the surface of nanoliposomes containing DSPC: DSPG: Cholesterol with/without DOPE. We observed that mice vaccinated with Lip-DOPE-P5+435 formulation had the highest number of IFN-γ- producing CTLs with the highest cytotoxic activity that consequently led to significantly smallest tumor size and prolonged survival rate in the TUBO mice model. In conclusion, our study indicated that the liposomal form of P5+435 peptide containing DOPE can be regarded as a promising prophylactic anti-cancer vaccine to generate potent antigen-specific immunity.

The Effect of Melatonin on Increasing the Health Related Quality of Life in Non-Metastatic Breast Cancer Patients: Three-Year Follow up a Clinical Trial

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Potential therapeutic effects of Ivermectin in COVID-19

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Smart Lipid-Based Nanosystems for Therapeutic Immune Induction against Cancers: Perspectives and Outlooks

“…DOPE was used to enable the fusion of liposomes, and presentation of antigens via phase transition induced in the acidic pH of endosomal compartments. Stronger immune responses with CTLs and tumor regression were detected in vivo [166,167]. ; TLR (Toll-like receptor); EPC (1,2-dioleoyl-sn-glycero-3-ethylphosphocholine); OVA (B16F10-OVA is a murine melanoma cell line expressing the chicken ovalbumin gene); gp70 RNA (Moloney murine leukemia virus); WES (whole-exome sequencing).…”