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.
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