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Liposomal Formulations of a Polyleucine朅ntigen Conjugate as Therapeutic Vaccines against Cervical Cancer
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Document Title
Liposomal Formulations of a Polyleucine朅ntigen Conjugate as Therapeutic Vaccines against Cervical Cancer
Author
Firdaus F.Z. Bartlett S. Hussein W.M. Lu L. Wright Q. Huang W. Nahar U.J. Yang J. Khongkow M. Veitch M. Koirala P. Ruktanonchai U.R. Monteiro M.J. Gonzalez Cruz J.L. Stephenson R.J. Wells J.W. Toth I. Skwarczynski M.
Affiliations
School of Chemistry and Molecular Biosciences The University of Queensland St. Lucia QLD 4072 Australia; Faculty of Medicine Frazer Institute The University of Queensland Brisbane QLD 4102 Australia; National Nanotechnology Center (NANOTEC) National Science and Technology Development Agency 111 Thailand Science Park Phahonyothin Rd. Khlong Luang Pathumthani 12120 Thailand; Australian Institute for Bioengineering and Nanotechnology The University of Queensland Brisbane QLD 4072 Australia; School of Pharmacy The University of Queensland Woolloongabba QLD 4102 Australia
Type
Article
Source Title
Pharmaceutics
ISSN
19994923
Year
2023
Volume
15
Issue
2
Open Access
All Open Access Gold Green
Publisher
MDPI
DOI
10.3390/pharmaceutics15020602
Abstract
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. ? 2023 by the authors.
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
License
CC BY
Rights
Authors
Publication Source
Scopus