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Clinical and Immune Responses in Resected Colon Cancer Patients Treated With Anti-Idiotype Monoclonal Antibody Vaccine That Mimics the Carcinoembryonic Antigen

From the Division of Hematology/Oncology, Department of Internal Medicine, and Barrett Cancer Center for Prevention, Treatment and Research, University of Cincinnati Medical Center, Cincinnati, and Oncology Hematology Care, Inc, Cincinnati, OH; Division of Hematology/Oncology, Department of Internal Medicine, and Lucille Parker Markey Cancer Center, University of Kentucky Medical Center, Lexington, KY; Titan Pharmaceuticals, Inc, South San Francisco, CA; and Aquila Biopharmacueticals, Framingham, MA.

Address reprint requests to Kenneth A. Foon, MD, Barrett Cancer Center, 234 Goodman St, ML 0502 Room 1097, Cincinnati, OH 45219-2316; emailkenneth.foon{at}uc.edu

PURPOSE: We generated an anti-idiotype antibody, designated CeaVac, that is an internal image of the carcinoembryonic antigen (CEA). We previously demonstrated that the majority of patients with advanced colorectal cancer generate specific anti-CEA responses. The purpose of the current study was to treat patients with surgically resected colon cancer with CeaVac to determine the immune response and clinical outcome to treatment with vaccine. We also compared the immune responses between patients treated with fluorouracil (5-FU) chemotherapy regimens plus vaccine versus vaccine alone.

PATIENTS AND METHODS: Thirty-two patients with resected Dukes' B, C, and D, and incompletely resected Dukes' D disease were treated with 2 mg of CeaVac every other week for four injections and then monthly until tumor recurrence or progression. Fourteen patients were treated concurrently with 5-FU chemotherapy regimens.

RESULTS: All 32 patients entered onto this trial generated high-titer immunoglobulin G and T-cell proliferative immune responses against CEA. The 5-FU regimens did not have a qualitative or quantitative effect on the immune response. Three of 15 patients with Dukes' B and C disease progressed at 19, 24, and 35 months. Seven of eight patients with completely resected Dukes' D disease remained on study from 12 to 33 months; one patient with resected Dukes' D disease relapsed at 9 months. One patient with incompletely resected Dukes' D disease remained on study at 14 months without evidence of progression; eight experienced disease progression at 6 to 31 months.

CONCLUSION: CeaVac consistently generated a potent anti-CEA humoral and cellular immune response in all 32 patients entered onto this trial. A number of very high-risk patients continue on study. 5-FU regimens, which are the standard of care for patients with Dukes' C disease, did not affect the immune response. These data warrant a phase III trial for patients with resected colon cancer.

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