Poly (I:C)-DOTAP cationic nanoliposome containing multi-epitope HER2-derived peptide promotes vaccine-elicited anti-tumor immunity in a murine model.
In the current study we aimed at developing a vaccine delivery/adjuvant system to enhance anti-tumor immunity against the natural multi-epitope HER2/Neu-derived P5 peptide. Polyriboinosinic: polyribocytidylic acid [Poly (I:C)] is a strong immunoadjuvant able to enhance specific antitumor immunity induced by peptide-based vaccines. Nevertheless, delivering the peptide and adjuvant intracellularly into their target site remains a challenging issue. We hypothesized this barrier could be overcome through the use of a cationic nanoliposome carrier system which can carry and protect the antigen and adjuvant in the extracellular environment and augment the induction of antitumor immunity. P5 was encapsulated in cationic nanoliposomes composed of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP)-Cholesterol either alone or complexed with Poly (I:C). Immunocompetent BALB/c mice were immunized with the formulations 3 times in two-week intervals and the efficiency and type of immune response were then evaluated both in vitro and in vivo. The groups immunized with Lip-P5+PIC (DOTAP-Cholestrol-P5+Poly (I:C)) and Lip+PIC (DOTAP-Cholestrol+Poly (I:C)) enhanced the release of Interferon (IFN)-γ in comparison with other groups. Flow cytometry analysis revealed that Lip-P5+PIC formulation induced the highest level of IFN-γ in CD8(+) lymphocytes. Lip-P5+PIC, Lip+PIC and Lip-P5 (DOTAP-Cholestrol-P5) provided some extent of protection in terms of tumor regression in TUBO tumor mice model during the first 65days post tumor challenge but at the end only the tumors of mice immunized with Lip-P5+PIC were significantly smaller than all other groups. Furthermore, tumors of mice receiving Lip-P5+PIC grew at a significantly slower rate throughout the observation period. Our results showed that the combination of Poly (I:C) and DOTAP with the tumor antigen and without applying additional T-helper epitope induced strong antitumor responses. The observations presented here are of great interest for future vaccine studies.
Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: ghazal.alipour@sydney.edu.au.
Ghazal
G
Alipour Talesh
Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Zahra
Z
Ebrahimi
Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Badieea@mums.ac.ir.
Ali
A
Badiee
Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Mercedeh
M
Mansourian
Department of Biochemical Engineering, Science & Research Branch Islamic Azad University, Tehran, Iran.
Hossein
H
Attar
Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Leila
L
Arabi
Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Immunology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: JalaliA@sbmu.ac.ir.
Seyed Amir
SA
Jalali
Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: Jafarimr@mums.ac.ir.
Mahmoud Reza
MR
Jaafari
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D005260:Female; D006801:Humans; D007109:Immunity; D007371:Interferon-gamma / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures / Q000737:chemistry; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D010446:Peptide Fragments / Q000276:immunology*; D011070:Poly I-C / Q000737:chemistry / Q000627:therapeutic use*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D005229:Fatty Acids, Monounsaturated; D007371:Interferon-gamma; D008081:Liposomes; D010446:Peptide Fragments; D011070:Poly I-C; D000644:Quaternary Ammonium Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases; C524056:Erbb2 protein, mouse; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane
Breast cancer vaccine; Cationic liposome; HER2/neu peptide immunotherapy; Peptide vaccine; Poly (I:C)