Lambda bacteriophage nanoparticles displaying GP2, a HER2/neu derived peptide, induce prophylactic and therapeutic activities against TUBO tumor model in mice

Atefeh Arab,Mahmoud Reza Jaafari,Atefeh Razazan,Fatemeh Mosaffa,Jessica Nicastro,Roderick Slavcev,Javad Behravan,Nastaran Barati

doi:10.1038/s41598-018-38371-z

Abstract

Generating a protective and long-lasting immune response is the primary goal in the expanding field of immunotherapeutic research. In current study we designed an immunogenic bacteriophage- based vaccine to induce a cytotoxic T lymphocyte activity against a mice tumor model over-expressing HER2/neu. Bacteriophage λ displaying a HER2/neu derived peptide GP2 was constructed and used as an anti-cancer vaccine in a BALB/c mouse xenograft tumor model. The results of our study indicated that phage nanoparticles displaying GP2 as a fused peptide to the gpD phage capsid protein induced a robust CTL response. Furthermore, the chimeric phage nanoparticles protected mice against HER2/neu-positive tumor challenge in both prophylactic and therapeutic settings. In conclusion, we propose that λ phage nanoparticles decorated with GP2 peptide merit further investigation for the development of peptide-based vaccines against HER2/neu overexpressing tumors.

Highlights

HER2/neu is a proto-oncogene that is overexpressed in 20–35% of human breast cancers[1]
This is advantageous when targeting self-antigens such as HER2 that mediate key biological functions in the body, as immune responses elicited by whole protein vaccines can stimulate the growth of tumor cells if the antibodies mimic the activity of growth factor ligands[16]
The vaccine reacted with the TUBO cells expressing rHER2/neu in comparison with the TN buffer (P < 0.01) and λ F7 groups (P < 0.05)

Summary

Introduction

HER2/neu is a proto-oncogene that is overexpressed in 20–35% of human breast cancers[1]. In 1988, the first use of phage particles to induce an immune response against the displayed foreign peptides was reported[15]. This is advantageous when targeting self-antigens such as HER2 that mediate key biological functions in the body, as immune responses elicited by whole protein vaccines can stimulate the growth of tumor cells if the antibodies mimic the activity of growth factor ligands[16]. Antigen-presenting cells (APCs) readily take and process the immunogenic molecule from the displaying phage This antigen specific targeting makes phages suitable delivery vehicles for immunization[18]

Objectives

Methods

Results

Conclusion