Title:Self-Adjuvanting Therapeutic Peptide-Based Vaccine Induce CD8+ Cytotoxic T Lymphocyte Responses in a Murine Human Papillomavirus Tumor Model
Volume: 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
Affiliation:
Keywords:
Cytotoxic T lymphocyte (CTL) responses, human papillomavirus, peptide subunit vaccine, polyacrylate, selfadjuvanting,
star-polymer, therapeutic anticancer vaccine.
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.