Poster Presentation 13th Australian Peptide Conference 2019

Polyacrylate-peptide liposomal formulation as a therapeutic vaccine candidate against cervical cancer (#156)

Waleed M Hussein 1 , Mattaka Khongkowa 2 , Tzu-Yu Liu 3 , Stacey Bartlett 1 , Reshma Nevagi 1 , Zhongfan Jia 4 , Michael J Monteiro 4 , James Wells 3 , Uracha Ruktanonchai 2 , Mariusz Skwarczynski 1 , Istvan Toth 1 4
  1. School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
  2. bNational Nanotechnology Center (NANOTEC), , National Science and Technology Development Agency, 111 Thailand Science Park, Phahonyothin Rd , Khlong Luang, Pathumthani, Thailand
  3. The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD, Australia
  4. Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, Australia

Peptide-based vaccines were proposed as a therapeutic strategy for many diseases, including cervical cancer associated with human papillomavirus (HPV). Peptide-based vaccines are a better treatment option than traditional chemotherapeutic agents and surgery because they rely on the immune system of the body to fight cancer cells, thereby minimizing the risk of side effects. However, it is essential to apply potent adjuvant and an appropriate delivery system to increase the efficacy of peptide-based vaccines. In this study, we developed a self-adjuvating delivery system for a therapeutic vaccine against cervical cancer based on a combination of polymer and liposomes. E7 HPV oncoprotein is unique to HPV-infected cells and is needed to maintain tumor cell growth associated with HPV. CD8 + peptide epitopes from E7 are therefore commonly used to activate cytotoxic T lymphocytes (CTLs) to develop cervical cancer vaccines. HPV-16 E7-derived peptide epitope: 8Qm (E744-57, QAEPDRAHYNIVTF) was conjugated to dendritic poly(tert-butyl acrylate) as a primary delivery system and incorporated into cationic liposomes as a secondary delivery system. Following a single immunization, our vaccine candidate was able to kill established HPV-16 E7-positive tumor (TC-1) cells in mice. After two months, the immunized mice had a survival rate of 80%.  By contrast, TC-1 tumors were not eradicated by both polymer-8Qm conjugate and 8Qm bearing liposomes. The survival rate of mice was only 20% when immunized with 8Qm formulated with standard incomplete Freund’s adjuvant.