TY - JOUR
T1 - Therapeutic human papillomavirus vaccines
T2 - Current clinical trials and future directions
AU - Hung, Chien Fu
AU - Ma, Barbara
AU - Monie, Archana
AU - Tsen, Shaw Wei
AU - Wu, T. C.
N1 - Funding Information:
The work is supported by the National Cancer Institute (NCI) specialized program of research excellence (SPORE) in Cervical Cancer P50 CA098252 and NCI 1RO1 CA114425-01.
PY - 2008/4
Y1 - 2008/4
N2 - Background: Cervical cancer is the second largest cause of cancer deaths in women worldwide. It is now evident that persistent infection with high-risk human papillomavirus (HPV) is necessary for the development and maintenance of cervical cancer. Thus, effective vaccination against HPV represents an opportunity to restrain cervical cancer and other important cancers. The FDA recently approved the HPV vaccine Gardasil for the preventive control of HPV, using HPV virus-like particles (VLP) to generate neutralizing antibodies against major capsid protein, L1. However, prophylactic HPV vaccines do not have therapeutic effects against pre-existing HPV infections and HPV-associated lesions. Furthermore, due to the considerable burden of HPV infections worldwide, it would take decades for preventive vaccines to affect the prevalence of cervical cancer. Thus, in order to speed up the control of cervical cancer and treat current infections, the continued development of therapeutic vaccines against HPV is critical. Therapeutic HPV vaccines can potentially eliminate pre-existing lesions and malignant tumors by generating cellular immunity against HPV-infected cells that express early viral proteins such as E6 and E7. Objective: This review discusses the future directions of therapeutic HPV vaccine approaches for the treatment of established HPV-associated malignancies, with emphasis on current progress of HPV vaccine clinical trials. Methods: Relevant literature is discussed. Results/conclusion: Though their development has been challenging, many therapeutic HPV vaccines have been shown to induce HPV-specific antitumor immune responses in preclinical animal models and several promising strategies have been applied in clinical trials. With continued progress in the field of vaccine development, HPV therapeutic vaccines may provide a potentially promising approach for the control of lethal HPV-associated malignancies.
AB - Background: Cervical cancer is the second largest cause of cancer deaths in women worldwide. It is now evident that persistent infection with high-risk human papillomavirus (HPV) is necessary for the development and maintenance of cervical cancer. Thus, effective vaccination against HPV represents an opportunity to restrain cervical cancer and other important cancers. The FDA recently approved the HPV vaccine Gardasil for the preventive control of HPV, using HPV virus-like particles (VLP) to generate neutralizing antibodies against major capsid protein, L1. However, prophylactic HPV vaccines do not have therapeutic effects against pre-existing HPV infections and HPV-associated lesions. Furthermore, due to the considerable burden of HPV infections worldwide, it would take decades for preventive vaccines to affect the prevalence of cervical cancer. Thus, in order to speed up the control of cervical cancer and treat current infections, the continued development of therapeutic vaccines against HPV is critical. Therapeutic HPV vaccines can potentially eliminate pre-existing lesions and malignant tumors by generating cellular immunity against HPV-infected cells that express early viral proteins such as E6 and E7. Objective: This review discusses the future directions of therapeutic HPV vaccine approaches for the treatment of established HPV-associated malignancies, with emphasis on current progress of HPV vaccine clinical trials. Methods: Relevant literature is discussed. Results/conclusion: Though their development has been challenging, many therapeutic HPV vaccines have been shown to induce HPV-specific antitumor immune responses in preclinical animal models and several promising strategies have been applied in clinical trials. With continued progress in the field of vaccine development, HPV therapeutic vaccines may provide a potentially promising approach for the control of lethal HPV-associated malignancies.
KW - Clinical trials
KW - HPV
KW - Human papillomavirus
KW - Therapeutic
KW - Vaccines
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UR - http://www.scopus.com/inward/citedby.url?scp=42149123438&partnerID=8YFLogxK
U2 - 10.1517/14712598.8.4.421
DO - 10.1517/14712598.8.4.421
M3 - Review article
C2 - 18352847
AN - SCOPUS:42149123438
SN - 1471-2598
VL - 8
SP - 421
EP - 439
JO - Expert Opinion on Biological Therapy
JF - Expert Opinion on Biological Therapy
IS - 4
ER -