Immune responses in advanced colorectal cancer following repeated intradermal vaccination with the anti-CEA murine monoclonal antibody, PR1A3: results of a phase I study
| Autor: | A. A. Epenetos, A. P. Zbar, W. A. Kmiot, M. Wadhwa, David Snary, T. G. Allen-Mersh, Elizabeth L. Ross, K. N. Syrigos, Walter F. Bodmer, P. Dilger, Robert W. Wilkinson, H. Thomas |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Injections Intradermal Antibodies Neoplasm Receptor expression medicine.medical_treatment Dose-Response Relationship Immunologic Cancer Vaccines Antibodies Monoclonal Murine-Derived Antigen Antigens Neoplasm Medicine Humans Hypersensitivity Delayed Alum adjuvant Immunity Mucosal Monoclonal antibody therapy Phytohaemagglutinin Aged Cell Proliferation Aged 80 and over biology business.industry Immune Sera Gastroenterology Antibodies Monoclonal Receptors Interleukin-2 Immunotherapy Middle Aged Antibodies Anti-Idiotypic Carcinoembryonic Antigen Treatment Outcome Case-Control Studies Immunology Monoclonal biology.protein Leukocytes Mononuclear Cytokines Female Antibody business Colorectal Neoplasms |
| Popis: | BACKGROUND AND AIMS: The aim was to determine the toxicity, clinical and immune responses to the murine monoclonal anti-carcinoembryonic antigen (CEA) antibody, PR1A3, in patients with advanced colorectal cancer. MATERIALS AND METHODS: Fifteen patients with advanced colorectal cancer received either 0.5-, 1.0- or 5.0-mg doses of PR1A3 mixed with 10% w/v Alum adjuvant (Superfos Biosector, Denmark) intradermally at 4-week intervals for 3 months. Patient serum was assessed for anti-idiotypic (Ab2), anti-anti-idiotypic (Ab3) and human anti-mouse antibody (HAMA) reactivity. Peripheral blood mononuclear cell (PBMC) proliferation with phytohaemagglutinin (PHA), CEA and PR1A3, stimulated IL-2, IL-4 and IFN-gamma levels and PR1A3-stimulated IL-2 receptor expression during immunotherapy were determined. Comparisons were made with 16 age-matched controls without malignant disease. RESULTS: Hyperimmune sera from 12 of the 15 patients showed Ab2 reactivity with no detectable Ab3 responses. Strong HAMA reactivity was recorded in 7 of the 15 cases with no adverse clinical effect. Delayed-type hypersensitivity (DTH) responses developed in 12 of the 15 patients. Pre-treatment PBMC proliferation with PHA was subnormal in each patient compared with controls, becoming normal (or supranormal) in all patients during immunisation (P |
| Databáze: | OpenAIRE |
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