Multiantigenic peptide-polymer conjugates as therapeutic vaccines against cervical cancer

Hussein, Waleed M., Liu, Tzu-Yu, Jia, Zhongfan, McMillan, Nigel A. J., Monteiro, Michael J., Toth, Istvan and Skwarczynski, Mariusz (2016) Multiantigenic peptide-polymer conjugates as therapeutic vaccines against cervical cancer. Bioorganic & Medicinal Chemistry, 24 18: 4372-4380. doi:10.1016/j.bmc.2016.07.036


Author Hussein, Waleed M.
Liu, Tzu-Yu
Jia, Zhongfan
McMillan, Nigel A. J.
Monteiro, Michael J.
Toth, Istvan
Skwarczynski, Mariusz
Title Multiantigenic peptide-polymer conjugates as therapeutic vaccines against cervical cancer
Journal name Bioorganic & Medicinal Chemistry   Check publisher's open access policy
ISSN 0968-0896
1464-3391
Publication date 2016-07-18
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.bmc.2016.07.036
Open Access Status Not Open Access
Volume 24
Issue 18
Start page 4372
End page 4380
Total pages 9
Place of publication Kidlington, Oxford, United Kingdom
Publisher Pergamon Press
Collection year 2017
Language eng
Formatted abstract
Immunotherapy is one of the most promising strategies for the treatment of cancer. Human papillomavirus (HPV) is responsible for virtually all cases of cervical cancer. The main purpose of a therapeutic HPV vaccine is to stimulate CD8+ cytotoxic T lymphocytes (CTLs) that can eradicate HPV infected cells. HPV oncoproteins E6 and E7 are continuously expressed and are essential for maintaining the growth of HPV-associated tumor cells. We designed polymer-based multi-antigenic formulations/constructs that were comprised of the E6 and E7 peptide epitopes. We developed an N-terminus-based epitope conjugation to conjugate two unprotected peptides to poly tert-butyl acrylate. This method allowed for the incorporation of the two antigens into a polymeric dendrimer in a strictly equimolar ratio. The most effective formulations eliminated tumors in up to 50% of treated mice. Tumor recurrence was not observed up to 3 months post initial challenge.
Keyword Cervical cancer
Human papillomavirus
Multiantigenic
Peptide-based subunit vaccine
Polymer–peptide conjugate
Self-adjuvanting
Therapeutic cancer vaccine
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Fri, 05 Aug 2016, 10:25:39 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences