Self adjuvanting polymer
Article pubs.acs.org/Biomac Self-Adjuvanting Polymer−Peptide Conjugates As Therapeutic
Vaccine Candidates against Cervical Cancer
Tzu-Yu Liu,† Waleed M. Hussein,† Zhongfan Jia,‡ Zyta M. Ziora,† Nigel A. J. McMillan,∥
Michael J. Monteiro,‡ Istvan Toth,†,§ and Mariusz Skwarczynski*,†
†
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia
∥
Cancer Research Centre, Griffith Health Institute and School of Medical Science, Griffith University, Gold Coast, QLD 4222,
Australia
§
School of Pharmacy, The University of Queensland, Brisbane, QLD 4072, Australia
‡
S
* Supporting Information
ABSTRACT: Dendrimers are structurally well-defined, synthetic polymers with sizes and physicochemical properties often resembling those of biomacromolecules (e.g., proteins).
As a result, they are promising candidates for peptide-based vaccine delivery platforms. Herein, we established a synthetic pathway to conjugate a human papillomavirus (HPV) E7 protein-derived peptide antigen to a star-polymer to create a macromolecular vaccine candidate to treat HPV-related cancers. These conjugates were able to reduce tumor growth and eradicate E7-expressing TC-1 tumors in mice after a single immunization, without the help of any external adjuvant.
■
INTRODUCTION
Vaccination is one of the most cost-effective public health interventions, and has been proposed as a promising strategy for the treatment of cancer.1 Cervical cancer results from the infection of the cervix with human papillomavirus (mainly HPV type 16), which disrupts the cell cycle through interaction between HPV proteins and the host cell.2 Prophylactic vaccines against HPV have been developed to prevent HPV infection
(and by extension, cervical cancer), achieving the best results if administered prior to the commencement of
Vaccine Candidates against Cervical Cancer
Tzu-Yu Liu,† Waleed M. Hussein,† Zhongfan Jia,‡ Zyta M. Ziora,† Nigel A. J. McMillan,∥
Michael J. Monteiro,‡ Istvan Toth,†,§ and Mariusz Skwarczynski*,†
†
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia
∥
Cancer Research Centre, Griffith Health Institute and School of Medical Science, Griffith University, Gold Coast, QLD 4222,
Australia
§
School of Pharmacy, The University of Queensland, Brisbane, QLD 4072, Australia
‡
S
* Supporting Information
ABSTRACT: Dendrimers are structurally well-defined, synthetic polymers with sizes and physicochemical properties often resembling those of biomacromolecules (e.g., proteins).
As a result, they are promising candidates for peptide-based vaccine delivery platforms. Herein, we established a synthetic pathway to conjugate a human papillomavirus (HPV) E7 protein-derived peptide antigen to a star-polymer to create a macromolecular vaccine candidate to treat HPV-related cancers. These conjugates were able to reduce tumor growth and eradicate E7-expressing TC-1 tumors in mice after a single immunization, without the help of any external adjuvant.
■
INTRODUCTION
Vaccination is one of the most cost-effective public health interventions, and has been proposed as a promising strategy for the treatment of cancer.1 Cervical cancer results from the infection of the cervix with human papillomavirus (mainly HPV type 16), which disrupts the cell cycle through interaction between HPV proteins and the host cell.2 Prophylactic vaccines against HPV have been developed to prevent HPV infection
(and by extension, cervical cancer), achieving the best results if administered prior to the commencement of
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