Combined synthetic and recombinant techniques for the development of lipoprotein-based, self-adjuvanting vaccines targeting human papillomavirus type-16 associated tumors

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Moyle, Peter M
Dai, Wei
Liu, Tzu-Yu
Hussein, Waleed M
Maruthayanar, Pirashanthini
Wells, James W
McMillan, Nigel AJ
Skwarczynski, Mariusz
Toth, Istvan
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2015
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Abstract

Human papillomaviruses (HPVs) are associated with various cancers, with HPV16 linked to more than half of cervical cancer cases. Vaccines to prevent HPV infection and cancer development have proven effective, but are not useful in individuals with prior HPV exposure. Treatment vaccines to eradicate or control HPV-associated lesions are therefore desirable for these patients. Herein we describe the development of a process to enable the production of semisynthetic vaccines based on the site-specific attachment of synthetic bacterial lipid analogs (e.g., Pam2Cys) to a non-oncogenic mutant HPV16 E7 protein to generate molecularly defined vaccines. Many cytotoxic lymphocyte (CTL) epitopes from E7 are delivered by this approach; potentially ensuring that large numbers of immunized individuals can generate CTLs to clear HPV infected cells. Delivery of this construct reduced the growth of HPV16-associated tumors in a TC1 mouse model, the effects of which were better than the potent CTL epitope HPV16 E7(44–57) administered with Montanide ISA51 adjuvant.

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Bioorganic & Medicinal Chemistry Letters

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25

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23

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© 2015 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.

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Medicinal and biomolecular chemistry

Medicinal and biomolecular chemistry not elsewhere classified

Organic chemistry

Pharmacology and pharmaceutical sciences

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