Oral Presentation 10th Australian Peptide Conference 2013

Peptide-Polymer Conjugates as Therapeutic Vaccine against Cervical Cancer (#23)

Mariusz Skwarczynski 1 , Tzu-Yu Liu 1 , Waleed M. Hussein 1 , Zhongfan Jia 2 , Nigel A. J. McMillan 3 , Michael J. Monteiro 2 , Istvan Toth 1
  1. School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia 4072, QLD, Australia
  2. Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane QLD 4072, QLD, Australia
  3. Cancer Research Centre, Griffith Health Institute and School of Medical Science, Griffith University, Gold Coast, QLD 4222, QLD, Australia

Cancer is the No. 1 killer of Australians. Cervical cancer remains third only to breast and ovarian cancer in terms of female cancer mortality worldwide. Only small increment in survival using chemotherapy has been witnessed. Immunotherapy has been proposed as one of the most attractive methods to reduce cancer mortality in human.1 Among the various immunotherapeutic delivery systems, peptide-based vaccines are simple, stable, well tolerated and can be tailored to produce the desired immunogenic effects.2 However such vaccines need delivery system and immunostimulant (adjuvant) to trigger desired immune responses.
We designed new vaccine delivery system-based on the polyacrylate polymer conjugated to peptide epitope. We applied this system to Group A Streptococcus (GAS) vaccine and have demonstrated that peptide subunit vaccine formulated into nanoparticle was able to induce desired humoral immune response in mice after single immunization when administered subcutaneously or intranasally without help of any external adjuvant.3-5
Recently, we applied this delivery strategy to create therapeutic peptide-based subunit anticancer vaccine. The synthesis of peptide epitopes was greatly improved by the change of standard SPPS procedure and application of the isopeptide method under microwave irradiation condition.6 The most promising antigens were identified, conjugated to polymer, and self-assembled into the particles. Modification of immunogenic epitope allowed the elimination of undesirable disulfide bond-based aggregation/polymerization of the peptide-polymers conjugates. Polyacrylate conjugated to the selected epitope produced excellent therapeutic effect against established tumour without help of any external adjuvant. This delivery system overcomes the lack of immunogenicity of peptide-based vaccines and common toxic side effect of external adjuvants. Noticeably, in contrast to many previously reported vaccine candidates, the conjugates demonstrated therapeutic effect after single immunization. Thus, we developed the first self-adjuvanting delivery system for the therapeutic vaccine against cervical cancer.

525-figure-APC-Mariusz.jpg

  1. Liu, T. Y.; Hussein, W. M.; Toth, I.; Skwarczynski, M. Advances in peptide-based human papillomavirus therapeutic vaccines. Curr. Top. Med.Chem. 2012, 12, 1581-1592.
  2. Skwarczynski, M.; Toth, I. Peptide-Based Subunit Nanovaccines. Current Drug Delivery 2011, 8, 282-289.
  3. Ahmad Fuaad, A. A. H.; Jia, Z.; Hartas, J.; Ziora, Z. M.; Lin, I. C.; Moyle, P. M.; Batzloff, M. R.; Good, M. F.; Monteiro, M. F.; Skwarczynski, M.; Toth, I. Polymer Peptide Hybrids as a Highly Immunogenic Single Dose Nanovaccine Nanomedicine 2013, in press.
  4. Zaman, M.; Skwarczynski, M.; Malcolm, J. M.; Urbani, C. N.; Jia, Z. F.; Batzloff, M. R.; Good, M. F.; Monteiro, M. J.; Toth, I. Self-adjuvanting polyacrylic nanoparticulate delivery system for group A streptococcus (GAS) vaccine. Nanomedicine-Nanotechnology Biology and Medicine 2011, 7, 168-173.
  5. Skwarczynski, M.; Zaman, M.; Urbani, C. N.; Lin, I. C.; Jia, Z. F.; Batzloff, M. R.; Good, M. F.; Monteiro, M. F.; Toth, I. Polyacrylate Dendrimer Nanoparticles: A Self-Adjuvanting Vaccine Delivery System. Angewandte Chemie-International Edition 2010, 49, 5742-5745.
  6. Hussein, W. M.; Liu, T. Y.; Toth, I.; Skwarczynski, M. Microwave-Assisted Synthesis of Difficult Sequence-Containing Peptide Using the Isopeptide Method. Organic & Biomolecular Chemistry 2013, in press.