4.7 Article

Multiantigenic peptide-polymer conjugates as therapeutic vaccines against cervical cancer

Journal

BIOORGANIC & MEDICINAL CHEMISTRY
Volume 24, Issue 18, Pages 4372-4380

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2016.07.036

Keywords

Peptide-based subunit vaccine; Multiantigenic; Human papillomavirus; Therapeutic cancer vaccine; Polymer-peptide conjugate; Self-adjuvanting; Cervical cancer

Funding

  1. National Health and Medical Research Council of Australia [NHMRC 1006454]

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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. (C) 2016 Elsevier Ltd. All rights reserved.

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