TY - JOUR
T1 - Polyacrylate-based delivery system for self-adjuvanting anticancer peptide vaccine
AU - Liu, Tzu Yu
AU - Hussein, Waleed M.
AU - Giddam, Ashwini Kumar
AU - Jia, Zhongfan
AU - Reiman, Jennifer M.
AU - Zaman, Mehfuz
AU - McMillan, Nigel A.J.
AU - Good, Michael F.
AU - Monteiro, Michael J.
AU - Toth, Istvan
AU - Skwarczynski, Mariusz
PY - 2014/12/9
Y1 - 2014/12/9
N2 - 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 "ingle 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.
AB - 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 "ingle 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.
KW - Polyacrylate-based
KW - Anticancer
KW - Peptide Vaccine
KW - Self-adjuvanting
UR - http://www.scopus.com/inward/record.url?scp=84921512451&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/NHMRC/1006454
U2 - 10.1021/jm501514h
DO - 10.1021/jm501514h
M3 - Article
C2 - 25489968
AN - SCOPUS:84921512451
SN - 0022-2623
VL - 58
SP - 888
EP - 896
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 2
ER -