Advances in dendritic-cell-based therapeutic vaccines for cervical cancer.
Cervical cancer is the second leading cause of cancer death among women worldwide and remains an important health problem for women, especially in underserved and minority groups in industrially developed nations. Although radical surgery and radiotherapy represent effective modalities of treatment for invasive cervical cancer, up to 35% of these patients overall will develop recurrent/metastatic disease for which treatment results remain poor. Novel therapeutic strategies that are effective in reducing the risk of recurrence/metastatic disease are still needed desperately. Human papillomavirus (HPV) infection represents the most important risk factor for the development of cervical dysplasia and cervical cancer. Since HPVE6 and E7 oncoproteins are constantly expressed in these lesions, these foreign proteins represent ideal tumor-specific target antigens for immunotherapy of cervical cancer. Recently, the recognition of dendritic cells (DC) as powerful antigen-presenting cells, capable of inducing primary T-cell responses in vitro and in vivo, has generated widespread interest in DC-based immunotherapy of several human malignancies. This review summarizes the therapeutic clinical trials and the different preclinical research strategies that are under investigation, with a particular emphasis on the use of autologous DC-pulsed HPV16 or 18 E7 oncoproteins as therapeutic vaccines against cervical cancer.
Bellone
Stefania
S
University of Arkansas for Medical Sciences, Department of Obstetrics & Gynecology, 4301 West Markham, Little Rock, AR 72205, USA. bellonestefania@uams.edu
Pecorelli
Sergio
S
Cannon
Martin J
MJ
Santin
Alessandro D
AD
D000328:Adult; D052685:Alphapapillomavirus / Q000276:immunology / Q000472:pathogenicity; D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000628:therapy; D009856:Oncogene Proteins, Viral / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000628:therapy; D010446:Peptide Fragments / Q000276:immunology; D012097:Repressor Proteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000628:therapy*
D000956:Antigens, Viral; D019496:Cancer Vaccines; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D010446:Peptide Fragments; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16