TY - JOUR
T1 - Multiantigenic peptide–polymer conjugates as therapeutic vaccines against cervical cancer
AU - Hussein, Waleed M.
AU - Liu, Tzu Yu
AU - Jia, Zhongfan
AU - McMillan, Nigel A.J.
AU - Monteiro, Michael J.
AU - Toth, Istvan
AU - Skwarczynski, Mariusz
PY - 2016/9/15
Y1 - 2016/9/15
N2 - 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.
AB - 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.
KW - Cervical cancer
KW - Human papillomavirus
KW - Multiantigenic
KW - Peptide-based subunit vaccine
KW - Polymer–peptide conjugate
KW - Self-adjuvanting
KW - Therapeutic cancer vaccine
UR - http://www.scopus.com/inward/record.url?scp=84982111782&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/NHMRC/1006454
U2 - 10.1016/j.bmc.2016.07.036
DO - 10.1016/j.bmc.2016.07.036
M3 - Article
C2 - 27475535
AN - SCOPUS:84982111782
VL - 24
SP - 4372
EP - 4380
JO - Bioorganic & Medicinal Chemistry
JF - Bioorganic & Medicinal Chemistry
SN - 0968-0896
IS - 18
ER -