P5 HER2/neu-derived peptide conjugated to liposomes containing MPL adjuvant as an effective prophylactic vaccine formulation for breast cancer

Author
Sheida Shariat, Ali Badiee, Seyed Jalali, Mercedeh Mansourian, Mona Yazdani, Seyed Mortazavi, Mahmoud Jaafari
Keywords
Abstract

Vaccines containing synthetic peptides derived from tumor-associated antigens (TAA) can elicit potent cytotoxic T lymphocyte (CTL) response if they are formulated in an optimal vaccine delivery system. The aim of this study was to develop a simple and effective lipid-based vaccine delivery system using P5 HER2/neu-derived peptide conjugated to Maleimide-PEG2000-DSPE. The conjugated lipid was then incorporated into liposomes composed of DMPC:DMPG:Chol:DOPE containing Monophosphoryl lipid A (MPL) (Lip-DOPE-P5-MPL). Different liposome formulations were prepared and characterized for their physicochemical properties. To evaluate anti-tumoral efficacy, BALB/c mice were immunized subcutaneously 3 times in two-week intervals and the generated immune response was studied. The results demonstrated that Lip-DOPE-P5-MPL induced a significantly higher IFN-γ production by CD8+ T cells intracellularly which represents higher CTL response in comparison with other control formulations. CTL response induced by this formulation caused the lowest tumor size and the longest survival time in a mice model of TUBO tumor. The encouraging results achieved by Lip-DOPE-P5-MPL formulation could make it a promising candidate in developing effective vaccines against Her2 positive breast cancers.

Year of Publication
2014
Journal
Cancer letters
Volume
355
Issue
1
Number of Pages
54-60
Date Published
12/2014
ISSN Number
1872-7980
DOI
10.1016/j.canlet.2014.09.016
Alternate Journal
Cancer Lett
PMID
25224570
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Reactivity
Mouse
Category
T cell ELISPOT
Analyte
IFN-γ, IL-4