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Volume 15
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10.3390/pharmaceutics15020602
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Article

Liposomal Formulations of a Polyleucine–Antigen Conjugate as Therapeutic Vaccines against Cervical Cancer

by
Farrhana Z. Firdaus
1,
Stacey Bartlett
1,
Waleed M. Hussein
1,
Lantian Lu
1,
Quentin Wright
2,
Wenbin Huang
1,
Ummey J. Nahar
1,
Jieru Yang
1,
Mattaka Khongkow
1,3,
Margaret Veitch
2,
Prashamsa Koirala
1,
Uracha R. Ruktanonchai
3,
Michael J. Monteiro
4,
Jazmina L. Gonzalez Cruz
2,
Rachel J. Stephenson
1,
James W. Wells
2,
Istvan Toth
1,5,* and
Mariusz Skwarczynski
1,*
1
School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia
2
Faculty of Medicine, Frazer Institute, The University of Queensland, Brisbane, QLD 4102, Australia
3
National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency, 111 Thailand Science Park, Phahonyothin Rd., Khlong Luang, Pathumthani 12120, Thailand
4
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia
5
School of Pharmacy, The University of Queensland, Woolloongabba, QLD 4102, Australia
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2023, 15(2), 602; https://doi.org/10.3390/pharmaceutics15020602
Submission received: 12 January 2023 / Revised: 6 February 2023 / Accepted: 8 February 2023 / Published: 10 February 2023
(This article belongs to the Special Issue Chemically Enhanced Peptide and Protein Therapeutics)
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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.
Keywords: cervical cancer; antitumor peptide vaccine; poly(amino acid); liposome; mannose-based targeting moiety cervical cancer; antitumor peptide vaccine; poly(amino acid); liposome; mannose-based targeting moiety
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MDPI and ACS Style

Firdaus, F.Z.; Bartlett, S.; Hussein, W.M.; Lu, L.; Wright, Q.; Huang, W.; Nahar, U.J.; Yang, J.; Khongkow, M.; Veitch, M.; et al. Liposomal Formulations of a Polyleucine–Antigen Conjugate as Therapeutic Vaccines against Cervical Cancer. Pharmaceutics 2023, 15, 602. https://doi.org/10.3390/pharmaceutics15020602

AMA Style

Firdaus FZ, Bartlett S, Hussein WM, Lu L, Wright Q, Huang W, Nahar UJ, Yang J, Khongkow M, Veitch M, et al. Liposomal Formulations of a Polyleucine–Antigen Conjugate as Therapeutic Vaccines against Cervical Cancer. Pharmaceutics. 2023; 15(2):602. https://doi.org/10.3390/pharmaceutics15020602

Chicago/Turabian Style

Firdaus, Farrhana Z., Stacey Bartlett, Waleed M. Hussein, Lantian Lu, Quentin Wright, Wenbin Huang, Ummey J. Nahar, Jieru Yang, Mattaka Khongkow, Margaret Veitch, and et al. 2023. "Liposomal Formulations of a Polyleucine–Antigen Conjugate as Therapeutic Vaccines against Cervical Cancer" Pharmaceutics 15, no. 2: 602. https://doi.org/10.3390/pharmaceutics15020602

APA Style

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. (2023). Liposomal Formulations of a Polyleucine–Antigen Conjugate as Therapeutic Vaccines against Cervical Cancer. Pharmaceutics, 15(2), 602. https://doi.org/10.3390/pharmaceutics15020602

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