The main goals of this project are to generate data concerning the biology of epithelial ovarian cancer (EOC) with a special emphasis on the identification and characterization of antigens characteristic of this tumor type. On-going studies have identified four antigenic systems particularly pertinent to EOC: 1) MX35 antigen; 2) CA-125 antigen; 3) mucin antigens, e.g., MUC-1; and 4) blood group-related specificities, such as Lewis. This project will emphasize the detailed biochemical , immunochemical, and molecular analysis of these antigens. MX35 antigen has been identified as a glycoprotein of 95,000 dalton and CA-125 as a mucin- type molecule. One goal will be to clone the genes coding for the protein portion of these molecules, with the aim of understanding their molecular makeup and perhaps function. For mucin antigens, we plan to analyze in detail the glycosylation characteristics of MUC-1 mucin and CA-125 antigen. The goal is to determine how glycosylation contributes to the tumor-specific of antibodies directed towards these antigens and whether mucin glycosylation is a tissue-specific characteristic. The experiments could also point towards new targets for the immunotherapy of EOC. A final goal will be to determine whether peptide mimics of carbohydrate epitopes characteristic of EOC, e.g., Le/y, can serve as vaccines for the development of anti-tumor responses. Overall, the project aims at understanding the immunogenicity of ovarian cancer and using this information to develop new therapeutic approaches.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA052477-08A1
Application #
6102611
Study Section
Project Start
1998-09-30
Project End
1999-07-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
8
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
Grisham, Rachel N; Sylvester, Brooke E; Won, Helen et al. (2015) Extreme Outlier Analysis Identifies Occult Mitogen-Activated Protein Kinase Pathway Mutations in Patients With Low-Grade Serous Ovarian Cancer. J Clin Oncol 33:4099-105
Rao, Thapi D; Tian, Huasong; Ma, Xun et al. (2015) Expression of the Carboxy-Terminal Portion of MUC16/CA125 Induces Transformation and Tumor Invasion. PLoS One 10:e0126633
Tew, William P; Colombo, Nicoletta; Ray-Coquard, Isabelle et al. (2014) Intravenous aflibercept in patients with platinum-resistant, advanced ovarian cancer: results of a randomized, double-blind, phase 2, parallel-arm study. Cancer 120:335-43
Tsuji, Takemasa; Sabbatini, Paul; Jungbluth, Achim A et al. (2013) Effect of Montanide and poly-ICLC adjuvant on human self/tumor antigen-specific CD4+ T cells in phase I overlapping long peptide vaccine trial. Cancer Immunol Res 1:340-50
Hyman, David M; Zhou, Qin; Iasonos, Alexia et al. (2012) Improved survival for BRCA2-associated serous ovarian cancer compared with both BRCA-negative and BRCA1-associated serous ovarian cancer. Cancer 118:3703-9
Marchini, Sergio; Poynor, Elizabeth; Barakat, Richard R et al. (2012) The zinc finger gene ZIC2 has features of an oncogene and its overexpression correlates strongly with the clinical course of epithelial ovarian cancer. Clin Cancer Res 18:4313-24
Iasonos, Alexia; Sabbatini, Paul; Spriggs, David R et al. (2012) Identifying clinical improvement in consolidation single-arm phase 2 trials in patients with ovarian cancer in second or greater clinical remission. Int J Gynecol Cancer 22:63-9
Soslow, Robert A; Han, Guangming; Park, Kay J et al. (2012) Morphologic patterns associated with BRCA1 and BRCA2 genotype in ovarian carcinoma. Mod Pathol 25:625-36
Blixt, Ola; Lavrova, Olga I; Mazurov, Dmitriy V et al. (2012) Analysis of Tn antigenicity with a panel of new IgM and IgG1 monoclonal antibodies raised against leukemic cells. Glycobiology 22:529-42
Gardner, Ginger J; Baser, Raymond E; Brady, Mark F et al. (2012) CA125 regression in ovarian cancer patients treated with intravenous versus intraperitoneal platinum-based chemotherapy: a gynecologic oncology group study. Gynecol Oncol 124:216-20

Showing the most recent 10 out of 109 publications