In vivo treatment with a monoclonal chimeric anti-CD4 antibody results in prolonged depletion of circulating CD4+ cells in chimpanzees
| Autor: | Margreet Jonker, G. Treacy, K. Y. Pak, A. F. Lobuglio, J. Iuliucci, S.H. Tam, E. Wilson, K. Bakker, P. van Eerd, W. Slingerland, P. E. Daddona, G. Riethmüller, Peter Rieber |
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| Rok vydání: | 1993 |
| Předmět: |
CD4-Positive T-Lymphocytes
Pan troglodytes Ratón medicine.drug_class medicine.medical_treatment Recombinant Fusion Proteins Immunology Biology Monoclonal antibody Lymphocyte Depletion Leukocyte Count Mice In vivo medicine Immunology and Allergy Animals Humans Immunity Cellular Immunogenicity Antibodies Monoclonal Immunotherapy Experimental Immunotherapy Hypersensitivity reaction Monoclonal Antibody Formation CD4 Antigens biology.protein Antibody |
| Zdroj: | Clinical and experimental immunology. 93(3) |
| ISSN: | 0009-9104 |
| Popis: | SUMMARY Chimeric M-T412 (cM-T412). an anti-CD4 antibody, was tolerated in chimpanzees at a dosage of 5 mg/kg per day for up to 7 consecutive days, or 5 mg/kg per dose, twice weekly for 4 weeks. All cM-T412-treated chimpanzees showed a prolonged CD4 cell depression. Weak chimpanzee antibody responses to chimeric M-T412 were observed. One of the chimpanzees on the biweekly dosage regimen exhibited a hypersensitivity reaction immediately after receiving its seventh dose. Following supportive treatment, the animal recovered and remained asymptomatic during the non-treatment observation period. The hypersensitivity reaction was not an unexpected response considering the animal received repeated intermittent i.v. administration of a foreign protein. This animal also showed a chimpanzee antibody response to chimeric M-T412 after the seventh dose. Chimeric M-T412 also induced an anti-cM-T412 response in some of the other animals. The level of this response was lower than the anti-mouse responses observed in animals treated with murinc anti-CD4. Moreover, the anti-cM-T4l 2 response was mainly directed to idiotypic determinants. The decrease in CD4+ cells observed for all chimeric M-T412-treated chimpanzees is an expected effect of the anti-CD4 antibody. The duration of this CD4+ cell decrease is. however, much longer than observed for other CD4-specific MoAbs described. No selective loss of either memory or naive CD4+ cells was observed after cither the single, 7-day or twice-weekly treatments. The CD4+ cell depression was reversible, although individual variation in time to recovery was observed. Therefore, cM-T412 could be a good candidate for clinical use in autoimmune conditions. |
| Databáze: | OpenAIRE |
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