In this project, two antibody-based approaches to the therapy of ovarian cancer are planned. One is based on active immunotherapy with conjugate vaccines and the other utilizes passive therapy with a radiolabeled antibody. Most ovarian cancers express at the cell surface GM2 ganglioside, the Thomsen-Friedenreich (TF), sialyl TN in cluster conformation (STN(C)), Lewis (Le/y) and Globo H carbohydrate antigens, the protein antigens MUC-1 and KSA, and the MX35 antigen. For well-defined carbohydrate and peptide antigens, conjugate vaccines have proven the most effective approach to augmenting the antibody response. Keyhole limpet hemocyanin (KLH) has been the most carrier molecule and the saponin fraction QS-21 the most immunological adjuvant. We now have KLH conjugate plus QS-21 vaccines capable of consistently inducing antibody responses in patients against GM2, sTn(C), Globo H, and MUC-1. A trial with Le/y is currently ongoing in ovarian cancer patients and trials with KSA and TF(C) conjugate vaccines are planned for the first half of 1998. The initial goals of Project III are to construct a consistently immunogenic polyvalent vaccine against ovarian cancer, to test this for immunogenicity and toxicity, and to compare systemic and intraperitoneal antibody titers after vaccination by the subcutaneous or intraperitoneal routes. A Phase II clinical trials with this polyvalent vaccine will be initiated late in the second year in patients with metastatic ovarian cancer who are free of grossly detectable disease after adjuvant chemotherapy, second-look surgery, and administration of intraperitoneal cisplatin and etoposide. The radio-labeled antibody 131/I MX35 F(ab')2 has been shown to localize to ovarian cancer peritoneal metastases when administered IP.A Phase I therapeutic trial is in progress; initial dosimetry results suggest significant therapeutic potential. Patients with visible disease (<1cm at second/look surgery) will be treated with 131/I-MX35 F(AB')2 in a second Phase II trial.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Sloan-Kettering Institute for Cancer Research
New York
United States
Zip Code
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