Immunomodulating IL-6 activity by murine monoclonal antibodies |
| |
| Institution: | 1. INSERM U291, 99 Rue Puech Villa, 34197 Montpellier Cedex 5, France;2. Institut de Biologie, BP1005, 44035 Nantes Cedex 1, France;3. IGMM, BP5051, 34033 Montpellier Cedex 1, France;1. Molecular Physiology Laboratory, Division of Physiology and Biochemistry, Central Sheep and Wool Research Institute, ICAR-CSWRI, Avikanagar, Rajasthan, 304501, India;2. Livestock Research Centre, Southren Regional Station, National Dairy Research Institute, ICAR-NDRI (SRS), Bengaluru, Karnataka, 560030, India;3. Animal Health Division, Central Sheep and Wool Research Institute, ICAR-CSWRI, Avikanagar, Rajasthan, 304501, India;4. Textile Manufacturing and Textile Chemistry Division, ICAR- Central Sheep and Wool Research Institute, Avikanagar, Rajasthan, 304501, India;5. Animal Biochemistry Division, National Dairy Research Institute, ICAR-NDRI, Karnal, Haryana, 132001, India;1. Cell Biology Group, Department of Experimental and Health Sciences, Pompeu Fabra University (UPF), CIBER on Neurodegenerative diseases (CIBERNED), Spain;2. Institute of Neurosciences and Department of Cellular Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Spain;1. Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China;2. Key Laboratory of Protein and Peptide Pharmaceuticals, CAS-University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Beijing, China;1. Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas;2. Cancer Biology Center, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas;3. Department of Biomedical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas;4. Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee;5. Department of Molecular Cell Biology and Toxicology, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China;6. Key Laboratory of Food Safety Research Center, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China;7. Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota;1. State Key Laboratory of Petroleum Resource and Prospecting, China University of Petroleum, Beijing 102200, China;2. College of Geosciences, China University of Petroleum, Beijing 102200, China;3. North China Company, SINOPEC, Zhengzhou, Henan 450006, China |
| |
| Abstract: | The human anti-mouse immunoglobulin antibody (HAMA) response, which occurs frequently after injection of murine monoclonal antibodies (MAb) directed against cellular targets, has been reported extensively in several studies. We analysed here HAMA in 12 patients (six with multiple myeloma, MM, and six with metastatic renal cell carcinoma, MRCC) who were treated with B-E8, an IgG1 MAb against interleukin-6 (IL-6). Efficiency of the treatment was evidenced by the drop in the serum levels of C reactive protein (CRP), of which the in vivo production is under the control of IL-6. Three patients with MM and the six patients with MRCC became immunized to the injected MAb. HAMA appeared between days 7 and 15 after the beginning of the treatment. The nine patients made IgG antibodies; four also made IgM. All of immunized patients made anti-idiotype antibodies specific to B-E8. Two of them also developed HAMA directed to murine IgG1 isotype; in these two patients B-E8 MAb cleared rapidly from the circulation with loss of treatment efficiency. In the patients who developed only anti-idiotype antibodies, serum levels of B-E8 remained unchanged and CRP production remained inhibited, indicating that treatment efficiency was not affected by the presence of HAMA. Circulating B-E8 MAb were still able to bind to IL-6 and to inhibit IL-6-independent proliferation despite the presence of anti-idiotypic HAMA. Therefore, in contrast to HAMA against MAb directed against cellular targets, HAMA against anti-IL-6 MAb idiotopes led neither to clearance nor to functional inactivation of the injected MAb. This was further shown by resuming the B-E8 treatment with success in a patient who still had anti-idiotypic HAMA. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
