Liposomal Formulations of a Polyleucine–Antigen Conjugate as Therapeutic Vaccines against Cervical Cancer
Farrhana Z. Firdaus,
Stacey Bartlett,
Waleed M. Hussein,
Lantian Lu,
Quentin Wright,
Wenbin Huang,
Ummey J. Nahar,
Jieru Yang,
Mattaka Khongkow,
Margaret Veitch,
Prashamsa Koirala,
Uracha R. Ruktanonchai,
Michael J. Monteiro,
Jazmina L. Gonzalez Cruz,
Rachel J. Stephenson,
James W. Wells,
Istvan Toth,
Mariusz Skwarczynski
Affiliations
Farrhana Z. Firdaus
School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia
Stacey Bartlett
School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia
Waleed M. Hussein
School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia
Lantian Lu
School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia
Quentin Wright
Faculty of Medicine, Frazer Institute, The University of Queensland, Brisbane, QLD 4102, Australia
Wenbin Huang
School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia
Ummey J. Nahar
School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia
Jieru Yang
School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia
Mattaka Khongkow
School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia
Margaret Veitch
Faculty of Medicine, Frazer Institute, The University of Queensland, Brisbane, QLD 4102, Australia
Prashamsa Koirala
School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia
Uracha R. Ruktanonchai
National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency, 111 Thailand Science Park, Phahonyothin Rd., Khlong Luang, Pathumthani 12120, Thailand
Michael J. Monteiro
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia
Jazmina L. Gonzalez Cruz
Faculty of Medicine, Frazer Institute, The University of Queensland, Brisbane, QLD 4102, Australia
Rachel J. Stephenson
School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia
James W. Wells
Faculty of Medicine, Frazer Institute, The University of Queensland, Brisbane, QLD 4102, Australia
Istvan Toth
School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia
Mariusz Skwarczynski
School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia
Human papilloma virus (HPV) is responsible for all cases of cervical cancer. While prophylactic vaccines are available, the development of peptide-based vaccines as a therapeutic strategy is still under investigation. In comparison with the traditional and currently used treatment strategies of chemotherapy and surgery, vaccination against HPV is a promising therapeutic option with fewer side effects. A peptide derived from the HPV-16 E7 protein, called 8Qm, in combination with adjuvants showed promise as a therapeutic vaccine. Here, the ability of polymerized natural amino acids to act as a self-adjuvating delivery system as a therapeutic vaccine was investigated for the first time. Thus, 8Qm was conjugated to polyleucine by standard solid-phase peptide synthesis and self-assembled into nanoparticles or incorporated in liposomes. The liposome bearing the 8Qm conjugate significantly increased mice survival and decreased tumor growth after a single immunization. Further, these liposomes eradicated seven-day-old well-established tumors in mice. Dendritic cell (DC)-targeting moieties were introduced to further enhance vaccine efficacy, and the newly designed liposomal vaccine was tested in mice bearing 11-day-old tumors. Interestingly, these DCs-targeting moieties did not significantly improve vaccine efficacy, whereas the simple liposomal formulation of 8Qm-polyleucine conjugate was still effective in tumor eradication. In summary, a peptide-based anticancer vaccine was developed that stimulated strong cellular immune responses without the help of a classical adjuvant.
