In order to select a suitable combination of cancer cell lines as an appropriate source of antigens for dendritic cell-based immunotherapy of ovarian cancer, we analyzed the expression level of 21 tumor associated antigens (BIRC5, CA125, CEA, DDX43, EPCAM, FOLR1, Her-2/neu, MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, MUC-1, NY-ESO-1, PRAME, p53, TPBG, TRT, WT1) in 4 established ovarian cancer cell lines and in primary tumor cells isolated from the high-grade serous epithelial ovarian cancer tissue. More than 90% of tumor samples expressed very high levels of CA125, FOLR1, EPCAM and MUC-1 and elevated levels of Her-2/neu, similarly to OVCAR-3 cell line. The combination of OV-90 and OVCAR-3 cell lines showed the highest overlap with patients' samples in the TAA expression profile.

Department of Immunology Charles University 2nd Faculty of Medicine University Hospital Motol Prague Czech Republic

Department of Obstetrics and Gynaecology Charles University 2nd Faculty of Medicine University Hospital Motol Prague Czech Republic

Research Department Sotio Prague Czech Republic

Zobrazit více v PubMed

Friedlander ML. Prognostic factors in ovarian cancer. Seminars in oncology. 1998;25:305–314. PubMed

Gilks CB. Subclassification of ovarian surface epithelial tumors based on correlation of histologic and molecular pathologic data. International journal of gynecological pathology. 2004;23:200–205. PubMed

Rosenthal AN, Jacobs IJ. The role of CA 125 in screening for ovarian cancer. The International journal of biological markers. 1998;13:216–220. PubMed

Bookman MA. Standard treatment in advanced ovarian cancer in 2005: the state of the art. International journal of gynecological cancer. 2005;15:212–220. PubMed

Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, Mannel RS, DeGeest K, Hartenbach EM, Baergen R, Gynecologic Oncology G Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. Journal of clinical oncology. 2003;21:3194–3200. PubMed

du Bois A, Luck HJ, Meier W, Adams HP, Mobus V, Costa S, Bauknecht T, Richter B, Warm M, Schroder W, Olbricht S, Nitz U, Jackisch C, Emons G, Wagner U, Kuhn W, et al. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. Journal of the National Cancer Institute. 2003;95:1320–1329. PubMed

Podrazil M, Horvath R, Becht E, Rozkova D, Bilkova P, Sochorova K, Hromadkova H, Kayserova J, Vavrova K, Lastovicka J, Vrabcova P, Kubackova K, Gasova Z, Jarolim L, Babjuk M, Spisek R, et al. Phase I/II clinical trial of dendritic-cell based immunotherapy (DCVAC/PCa) combined with chemotherapy in patients with metastatic, castration-resistant prostate cancer. Oncotarget. 2015;6:18192–18205. doi: 10.18632/oncotarget.4145. PubMed DOI PMC

Canney PA, Moore M, Wilkinson PM, James RD. Ovarian cancer antigen CA125: a prospective clinical assessment of its role as a tumour marker. British journal of cancer. 1984;50:765–769. PubMed PMC

Shi JX, Qin JJ, Ye H, Wang P, Wang KJ, Zhang JY. Tumor associated antigens or anti-TAA autoantibodies as biomarkers in the diagnosis of ovarian cancer: a systematic review with meta-analysis. Expert review of molecular diagnostics. 2015;15:829–852. PubMed

Bellone S, Siegel ER, Cocco E, Cargnelutti M, Silasi DA, Azodi M, Schwartz PE, Rutherford TJ, Pecorelli S, Santin AD. Overexpression of epithelial cell adhesion molecule in primary, metastatic, and recurrent/chemotherapy-resistant epithelial ovarian cancer: implications for epithelial cell adhesion molecule-specific immunotherapy. International journal of gynecological cancer. 2009;19:860–866. PubMed

Schwab CL, English DP, Roque DM, Pasternak M, Santin AD. Past, present and future targets for immunotherapy in ovarian cancer. Immunotherapy. 2014;6:1279–1293. PubMed PMC

Kim DK, Lee TV, Castilleja A, Anderson BW, Peoples GE, Kudelka AP, Murray JL, Sittisomwong T, Wharton JT, Kim JW, Ioannides CG. Folate binding protein peptide 191-199 presented on dendritic cells can stimulate CTL from ovarian and breast cancer patients. Anticancer research. 1999;19:2907–2916. PubMed

Peoples GE, Anderson BW, Lee TV, Murray JL, Kudelka AP, Wharton JT, Ioannides CG. Vaccine implications of folate binding protein, a novel cytotoxic T lymphocyte-recognized antigen system in epithelial cancers. Clinical cancer research. 1999;5:4214–4223. PubMed

Knutson KL, Krco CJ, Erskine CL, Goodman K, Kelemen LE, Wettstein PJ, Low PS, Hartmann LC, Kalli KR. T-cell immunity to the folate receptor alpha is prevalent in women with breast or ovarian cancer. Journal of clinical oncology. 2006;24:4254–4261. PubMed

Ioannides CG, Fisk B, Jerome KR, Irimura T, Wharton JT, Finn OJ. Cytotoxic T cells from ovarian malignant tumors can recognize polymorphic epithelial mucin core peptides. Journal of immunology. 1993;151:3693–3703. PubMed

Rahma OE, Ashtar E, Czystowska M, Szajnik ME, Wieckowski E, Bernstein S, Herrin VE, Shams MA, Steinberg SM, Merino M, Gooding W, Visus C, Deleo AB, Wolf JK, Bell JG, Berzofsky JA, Whiteside TL, Khleif SN. A gynecologic oncology group phase II trial of two p53 peptide vaccine approaches: subcutaneous injection and intravenous pulsed dendritic cells in high recurrence risk ovarian cancer patients. Cancer Immunology, Immunotherapy. 2011;61:373–384. PubMed PMC

Knutson KL, Disis ML. Expansion of HER2/neu-specific T cells ex vivo following immunization with a HER2/neu peptide-based vaccine. Clinical breast cancer. 2001;2:73–79. PubMed

Kobayashi M, Chiba A, Izawa H, Yanagida E, Okamoto M, Shimodaira S, Yonemitsu Y, Shibamoto Y, Suzuki N, Nagaya M, DC-vaccine study group at the Japan Society of Innovative Cell Therapy (J-SICT) The feasibility and clinical effects of dendritic cell-based immunotherapy targeting synthesized peptides for recurrent ovarian cancer. Journal of Ovarian Research. 2014;7:48. PubMed PMC

Induction of Tolerance and Immunity by Dendritic Cells: Mechanisms and Clinical Applications