title: Clinical and immune responses in advanced colorectal cancer patients treated with anti-idiotype monoclonal antibody vaccine that mimics the carcinoembryonic antigen.
abstract: Carcinoembryonic antigen (CEA) is expressed in a wide variety of adenocarcinomas, and it is well recognized that cancer patients are immunologically "tolerant" to CEA. The purpose of this study was to determine whether we could break immune tolerance to CEA by vaccinating patients with a monoclonal anti-idiotype antibody that is the internal image of CEA and to determine what impact this might have on patient survival. Twenty-four patients with advanced CEA-positive colorectal cancer who failed standard therapies except for two were entered into this Phase Ib trial. One patient was considered not assessable, because on the day of entering into the study, she was diagnosed with acute myelogenous leukemia. Patients were treated with 1, 2, or 4 mg of aluminum hydroxide-precipitated 3H1 anti-idiotype antibody every other week for four injections and then monthly until tumor progression was observed. Immunological monitoring included humoral and cellular idiotypic and CEA responses, and all patients were evaluated for toxicity, response, and survival. Hyperimmune sera from 17 of 23 patients demonstrated an anti-anti-idiotypic Ab3 response, and 13 of these responses were demonstrated to be true anti-CEA responses (Ab1'). The antibody response was polyclonal, and 11 mediated antibody-dependent cellular cytotoxicity. Ten patients had idiotypic T-cell responses, and five had specific T-cell responses to CEA. None of the patients had objective clinical responses, but overall median survival for the 23 evaluable patients was 11.3 months, with 44% 1-year survival (95% confidence interval, 23-64%). Toxicity was limited to local swelling and minimal pain. Anti-idiotype monoclonal antibody 3H1 that mimics CEA was able to break immune tolerance in the majority of treated patients. Overall survival of 11.3 months was comparable to other phase II data with advanced colorectal cancer patients treated with a variety of chemotherapy agents, including irinotecan, with considerably less toxicity. Although it is not clear that the vaccine itself had an impact on survival, this should be determined in a Phase III randomized trial.
authors.affiliation: Lucille Parker Markey Cancer Center, Department of Internal Medicine, Division of Hematology/Oncology, University of Kentucky Medical Center, Lexington, Kentucky 40536, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Foon
authors.forename: W J
authors.initials: WJ
authors.lastname: John
authors.forename: M
authors.initials: M
authors.lastname: Chakraborty
authors.forename: A
authors.initials: A
authors.lastname: Sherratt
authors.forename: J
authors.initials: J
authors.lastname: Garrison
authors.forename: M
authors.initials: M
authors.lastname: Flett
authors.forename: M
authors.initials: M
authors.lastname: Bhattacharya-Chatterjee
mesh_terms: D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D000910:Antibodies, Heterophile / Q000097:blood; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D001323:Autoantibodies / Q000097:blood; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen / Q000097:blood / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018579:Patient Selection; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000910:Antibodies, Heterophile; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen