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Lambda phage nanoparticles displaying HER2-derived E75 peptide induce effective E75-CD8+ T response.

Atefeh Arab1, Jessica Nicastro2,3, Roderick Slavcev2,3,4

  • 1Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Immunologic Research
|November 17, 2017
PubMed
Summary

This study explored a phage-based vaccine targeting HER2 in breast cancer. While showing immune response in vitro, it had limited therapeutic effect in vivo, possibly due to regulatory T cells.

Keywords:
E75 peptideHER2/neu proteinLambda (λ)Phage displayλF7

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Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • The human epidermal growth factor receptor 2 (HER2) is a target in breast cancer therapy.
  • Bacteriophage display systems offer a novel platform for vaccine development.

Purpose of the Study:

  • To evaluate the immunogenicity and therapeutic potential of lambda phage particles displaying the E75 peptide (derived from HER2) in a mouse breast tumor model.
  • To investigate the prophylactic and therapeutic efficacy of the phage-based vaccine.

Main Methods:

  • Immunization of BALB/c mice with E75-displaying phage (λF7-gpD::E75) at 2-week intervals over 6 weeks.
  • Assessment of in vitro immune responses and in vivo tumor growth and survival.
  • Analysis of regulatory T cell populations (Foxp3+ CD4+CD25+).

Main Results:

  • λF7-gpD::E75 induced immune responses in vitro compared to controls.
  • No significant prophylactic effect observed; all mice developed tumors.
  • Therapeutic immunization showed a significant reduction in tumor size and prolonged survival (P < 0.05).
  • Discrepancy between in vitro and in vivo results noted.

Conclusions:

  • The phage-based vaccine demonstrated in vitro immunogenicity but limited in vivo anti-tumor efficacy.
  • The presence of regulatory T cells (Foxp3+ CD4+CD25+) may have impaired the therapeutic anti-tumor response.