Self-adjuvanting therapeutic peptide-based vaccine induce CD8+ cytotoxic T lymphocyte responses in a murine human papillomavirus tumor model

Curr Drug Deliv. 2015;12(1):3-8. doi: 10.2174/1567201811666141001155729.

Abstract

Vaccine candidates for the treatment of human papillomavirus (HPV)-associated cancers are aimed to activate T-cells and induce development of cytotoxic anti-tumor specific responses. Peptide epitopes derived from HPV-16 E7 oncogenic protein have been identified as promising antigens for vaccine development. However, peptide-based antigens alone elicit poor cytotoxic T lymphocyte (CTL) responses and need to be formulated with an adjuvant (immunostimulant) to achieve the desired immune responses. We have reported the ability of polyacrylate 4-arm star-polymer (S4) conjugated with HPV-16 E744-57 (8Qmin) epitope to reduce and eradicate TC-1 tumor in the mouse model. Herein, we have studied the mechanism of induction of immune responses by this polymer-peptide conjugate and found prompt uptake of conjugate by antigen presenting cells, stimulating stronger CD8(+) rather than CD4(+) or NK cell responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylic Resins / chemistry
  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / chemistry
  • Animals
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / chemistry
  • Cancer Vaccines / immunology
  • Cell Line, Tumor
  • Chemistry, Pharmaceutical
  • Drug Carriers
  • Epitopes
  • Female
  • Immunization
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / virology
  • Mice, Inbred C57BL
  • Molecular Structure
  • Papillomavirus E7 Proteins / administration & dosage*
  • Papillomavirus E7 Proteins / chemistry
  • Papillomavirus E7 Proteins / immunology
  • Papillomavirus Infections / drug therapy*
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / virology
  • Papillomavirus Vaccines / administration & dosage*
  • Papillomavirus Vaccines / chemistry
  • Papillomavirus Vaccines / immunology
  • T-Lymphocytes, Cytotoxic / drug effects*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / virology
  • Technology, Pharmaceutical / methods

Substances

  • Acrylic Resins
  • Adjuvants, Immunologic
  • Cancer Vaccines
  • Drug Carriers
  • Epitopes
  • Papillomavirus E7 Proteins
  • Papillomavirus Vaccines
  • oncogene protein E7, Human papillomavirus type 16
  • carbopol 940