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Self-Adjuvanting Therapeutic Peptide-Based Vaccine Induce CD8+ Cytotoxic T Lymphocyte Responses in a Murine Human Papillomavirus Tumor Model

[ Vol. 12 , Issue. 1 ]

Author(s):

Tzu-Yu Liu, Ashwini Kumar Giddam, Waleed M. Hussein, Zhongfan Jia, Nigel A.J. McMillan, Michael J. Monteiro, Istvan Toth and Mariusz Skwarczynski   Pages 3 - 8 ( 6 )

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.

Keywords:

Cytotoxic T lymphocyte (CTL) responses, human papillomavirus, peptide subunit vaccine, polyacrylate, selfadjuvanting, star-polymer, therapeutic anticancer vaccine.

Affiliation:

School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia.



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