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

Immunol Res. 2018 Feb;66(1):200-206. doi: 10.1007/s12026-017-8969-0.

Abstract

We have investigated the in vitro immunogenicity and in vivo prophylactic and therapeutic potential of lambda (λ) phage particles displaying the E75 peptide (derived from HER2 protein) in an implantable TUBO breast tumor model of BALB/c mice. The mice were immunized with the E75-displaying phage (λF7-gpD::E75) every 2-week intervals over a 6-week period, and the generated immune responses were studied. Results showed in vitro induction of immune responses by the λF7 (gpD::E75) construct compared to the control λF7 and buffer groups. In the in vivo prophylactic study, all the control and vaccinated mice groups developed tumors. However, in the therapeutic experiments, we observed a significant difference in tumor size at days 14-36 for mice immunized with λF7 (gpD::E75) compared to control groups (P < 0.05). Moreover, the survival time prolonged in mice immunized with λF7 (gpD::E75). The discrepancy between the results obtained from the in vitro and in vivo studies may have been a result of the induction of Foxp3 CD4+CD25+ which has been previously reported to hamper effective T cell functionality. In conclusion, we observed a significant immune stimulatory response in the in vitro study, while in vivo, the vaccine was not able to exert significant tumor inhibitory effects. We suggest that the presence of Foxp3+ CD4+CD25+ cells may have impaired the anti-tumor response in mice challenged in vivo with the TUBO xenograft tumor.

Keywords: E75 peptide; HER2/neu protein; Lambda (λ); Phage display; λF7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteriophage lambda / physiology*
  • Breast Neoplasms / therapy*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Disease Models, Animal
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Forkhead Transcription Factors / metabolism
  • Glucosephosphate Dehydrogenase / genetics
  • Glucosephosphate Dehydrogenase / immunology*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology*
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Tumor Burden
  • Vaccination

Substances

  • Epitopes, T-Lymphocyte
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • HER2 peptide (369-377)
  • Peptide Fragments
  • Glucosephosphate Dehydrogenase
  • Receptor, ErbB-2