Self-Adjuvanting Peptide Vaccines Against Cervical Cancer
*Corresponding author: Hannah Hanh-Hong Truong, Waleed M. Hussein*, Tzu-Yu Liu, Zhongfan Jia, James W. Wells, Michael J. Monteiro, Mariusz Skwarczynski and Istvan Toth
Cervical cancer is a common cause of cancer-related deaths in women worldwide, with a fatality rate second only to breast cancer. Human papillomaviruses (HPVs) are the main causative agents of cervical cancer, and are therefore obvious targets for vaccine development. Although two prophylactic HPV vaccines have been commercialized, therapeutic vaccines against HPVs have not been developed yet. Current vaccine technologies emphasize the power of small particles in targeting immune cells, and particles of 20-50 nm have been reported to induce optimal immune responses against a variety of pathogens and cancers.
We synthesized new nanoparticle-based vaccines against cervical cancer by using antigenic 8Qmin peptide epitope derived from HPV-16 E7 protein, a hydrophilic poly-(L-glutamic acid) (PGA) linker, and an 8-arm poly (tert-butyl acrylate) dendrimer-based delivery system (D8).
Four different peptides containing 8Qmin and PGA of different lengths were successfully synthesized with high yield and purity. These were then conjugated to alkyne-functionalized D8 by copper-catalyzed alkyne-azide cycloaddition “click” reaction. The conjugates self-assembled into nanoparticles, with decreased particle size corresponding to a greater number of Glu units. The four vaccine candidates were tested in C57 black 6 (C57BL/6) mice bearing well-established (7-day-old) tumors to examine their therapeutic effects.
Interestingly, only one conjugate delayed tumor growth, and montanide adjuvanted antigen, used as a positive control, failed to demonstrate any therapeutic effect.
Peptide-based subunit vaccine; Human papillomavirus; Polyglutamic acid; Therapeutic cancer vaccine; Polymer-peptide conjugate; Self-adjuvanting; Cervical cancer.