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

Tzu-Yu Liu; Ashwini Kumar Giddam; Waleed M Hussein; Zhongfan Jia; Nigel A J McMillan; Michael J Monteiro; Istvan Toth; Mariusz Skwarczynski

doi:10.2174/1567201811666141001155729

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.

Authors

Tzu-Yu Liu, Ashwini Kumar Giddam, Waleed M Hussein, Zhongfan Jia, Nigel A J McMillan, Michael J Monteiro, Istvan Toth, Mariusz Skwarczynski¹

Affiliation

¹ School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia. [email protected].

PMID: 25269453
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