Back to Search Start Over

Polyacrylate-Based Delivery System for Self-adjuvanting Anticancer Peptide Vaccine

Authors :
Nigel A.J. McMillan
Jennifer M. Reiman
Michael F. Good
Istvan Toth
Mehfuz Zaman
Waleed M. Hussein
Ashwini Kumar Giddam
Zhongfan Jia
Michael J. Monteiro
Tzu-Yu Liu
Mariusz Skwarczynski
Source :
Journal of Medicinal Chemistry. 58:888-896
Publication Year :
2014
Publisher :
American Chemical Society (ACS), 2014.

Abstract

Vaccination can provide a safe alternative to chemotherapy by using the body's natural defense mechanisms to create a potent immune response against tumor cells. Peptide-based therapeutic vaccines against human papillomavirus (HPV)-related cancers are usually designed to elicit cytotoxic T cell responses by targeting the HPV-16 E7 oncoprotein. However, peptides alone lack immunogenicity, and an additional adjuvant or external delivery system is required. In this study, we developed new polymer-peptide conjugates to create an efficient self-adjuvanting system for peptide-based therapeutic vaccines. These conjugates reduced tumor growth and eradicated E7-positive TC-1 tumors in mice after a "single shot" immunization, without the help from an external adjuvant. The new conjugates had a significantly higher anticancer efficacy than the antigen formulated with a commercial adjuvant. Furthermore, the polymer-peptide conjugates were promptly taken up by antigen presenting cells, including dendritic cells and macrophages, and efficiently activated CD4(+) T-helper cells and CD8(+) cytotoxic T lymphocyte cells.

Details

ISSN :
15204804 and 00222623
Volume :
58
Database :
OpenAIRE
Journal :
Journal of Medicinal Chemistry
Accession number :
edsair.doi.dedup.....5ae35f482705db8f905087d2dbcc72b8
Full Text :
https://doi.org/10.1021/jm501514h