Preparation of nanoliposomes linked to HER2/neu‐derived (P5) peptide containing MPL adjuvant as vaccine against breast cancer

Abstract

The study was aimed at evaluating antitumor and immunomodulatory effects of liposomal vaccine composed of P5 human epidermal growth factor receptor 2 (HER2)/neu‐derived peptide coupled to the surface of high‐temperature nanoliposomes containing distearoylphosphocholine:distearoylphosphoglycerol:Chol:dioleoylphosphatidylethanolamine (DOPE) comprising monophosphoryl lipid A (MPL) adjuvant in HER2/neu overexpressing the breast cancer model. BALB/c mice bearing TUBO carcinoma were subcutaneously immunized with formulations containing 10 µg P5 peptide and 25 µg MPL three times with 2‐week intervals. To determine immuno responses in immunized mice, the amount of released interferon‐γ and IL‐4 were measured by the enzyme‐linked immunospot method and the flow cytometric analysis on the isolated splenocytes. The results demonstrated that tumor‐bearing mice immunized with Lip/DOPE/MPL/P5 formulation had the most released interferon‐γ and the highest cytotoxic T lymphocyte responses that led to the lowest tumor size and the longest survival time than those of other formulations. The results achieved by Lip/DOPE/MPL/P5 formulation could make it a suitable candidate to induce effective antigen‐specific tumor immunity against breast cancer.

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

“…In this way, the use of DOPE-contained nanoliposomes, as a pH-sensitive and fusogenic liposome, is an effective tool for cytosol delivery and assembling of the peptide into the MHC class I pathway, which leads to the activation of CTLs response [15,[20][21][22][23]. Our earlier studies show that the inclusion of pH-sensitive lipids, such as DOPE, in the liposomal formulation used as a cancer vaccine can efficiently induce cell-mediated immunity [6,[28][29][30].…”

“…https://doi.org/10.1371/journal.pone.0243550.g004 CD8 mediated immunity [6,25,29,30]. Besides, nanoliposomes with high transition temperature phospholipids were also potent in inducing T helper 1 (Th1) cellular responses [18,25].…”

“…Therefore, in further studies, the P5 peptide was linked to Maleimide-PEG2000-DSPE via a covalent bond, which was associated with enhanced incorporation of the peptide into liposomes [6,28]. It was shown in our previous studies that the conjugated form of P5 and P435 peptides, as a liposomal peptide vaccine could lead to effective CTL responses [29,30]. In this study, we conjugated two multi-epitope peptides, P5 and P435.…”

The Peptide Vaccine of the Future

“…However, the prototype among TLR4 ligands -by guest on December 13, 2020 lipopolysaccharide (LPS) -is not sustainable for clinical application due to substantial toxicity 104,105 . Its chemically detoxified form MPL (3-O-desacyl-4'-monophosphoryl lipid A) 106 is an approved adjuvant for example in human papillomavirus (HPV) vaccines and furthermore investigated in different vaccination approaches 107,108 . The most commonly used TLR agonist 71 Further improvement of imaging technologies to track either the peptide vaccine at the molecular and (sub)cellular level 112 or the peptide-specific T cells in the organism 113 will further expand our knowledge of antigen delivery, uptake and processing as well as of antigen-specific T-cell routes.…”

“…However, the prototype among TLR4 ligands—lipopolysaccharide (LPS)—is not sustainable for clinical application owing to substantial toxicity ( 104 , 105 ). Its chemically detoxified form MPL (3-O-desacyl-4’-monophosphoryl lipid A) ( 106 ) is an approved adjuvant, for example, in human papillomavirus vaccines and furthermore investigated in different vaccination approaches ( 107 , 108 ). The most commonly used TLR agonist ( 71 ) poly-ICLC (Hiltonol) is a polyinosinic-polycytidylic acid (poly-IC) stabilized by lysine and carboxymethylcellulose ( 109 ), which enhances vaccine-induced T cell responses ( 110 ) by TLR3 signaling.…”