Antigen-specific immunotherapy of cervical and ovarian cancer.
We contrast the efforts to treat ovarian cancer and cervical cancer through vaccination because of their different pathobiology. A plethora of approaches have been developed for therapeutic vaccination against cancer, many of which target defined tumor-associated antigens (TAAs). Persistent infection with oncogenic human papillomavirus (HPV) types causes cervical cancer. Furthermore, cervical cancer patients frequently mount both humoral and T-cell immune responses to the HPV E6 and E7 oncoproteins, whose expression is required for the transformed phenotype. Numerous vaccine studies target these viral TAAs, including recent trials that may enhance clearance of pre-malignant disease. By contrast, little is known about the etiology of epithelial ovarian cancer. Although it is clear that p53 mutation or loss is a critical early event in the development of epithelial ovarian cancer, no precursor lesion has been described for the most common serous histotype, and even the location of its origin is debated. These issues have complicated the selection of appropriate ovarian TAAs and the design of vaccines. Here we focus on mesothelin as a promising ovarian TAA, because it is overexpressed and immunogenic at high frequency in patients, is displayed on the cell surface, and potentially contributes to ovarian cancer biology.
Hung
Chien-Fu
CF
Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, MD 21231, USA.
Wu
T C
TC
Monie
Archana
A
Roden
Richard
R
D000957:Antigens, Viral, Tumor / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; D003713:Dendritic Cells; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D058851:GPI-Linked Proteins; D005822:Genetic Vectors; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods*; D047908:Intracellular Signaling Peptides and Proteins; D016246:Lymphocytes, Tumor-Infiltrating; D008562:Membrane Glycoproteins / Q000276:immunology*; D000090204:Mesothelin; D009365:Neoplasm Regression, Spontaneous; D009367:Neoplasm Staging; D009856:Oncogene Proteins, Viral / Q000276:immunology; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D050725:Papillomavirus E7 Proteins / Q000276:immunology; D030361:Papillomavirus Infections / Q000150:complications / Q000276:immunology; D011237:Predictive Value of Tests; D011506:Proteins / Q000276:immunology; D050378:T-Lymphocytes, Regulatory; D016159:Tumor Suppressor Protein p53 / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy
D000957:Antigens, Viral, Tumor; D001323:Autoantibodies; D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; C466080:E6 protein, human papillomavirus type 1; D000939:Epitopes; D058851:GPI-Linked Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C549756:NBR1 protein, human; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011506:Proteins; D016159:Tumor Suppressor Protein p53; D000090204:Mesothelin