Differential Effects of Administration of a Human Anti-CD4 Monoclonal Antibody, HM6G, in Nonhuman Primates
| Autor: | Dianne M. Fishwild, Ada H. C. Kung, Debra Hudson, Usha Deshpande |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
CD4-Positive T-Lymphocytes
Primates Anti-CD4 Monoclonal Antibody Pan troglodytes CD4 antigen medicine.drug_class medicine.medical_treatment Immunology Cell Count CHO Cells Monoclonal antibody Mice chemistry.chemical_compound Immune system Cricetinae biology.animal medicine Animals Humans Immunology and Allergy Primate Avidity biology Antibodies Monoclonal Immunotherapy T lymphocyte Kinetics Macaca fascicularis chemistry CD4 Antigens |
| Zdroj: | Clinical Immunology. 92:138-152 |
| ISSN: | 1521-6616 |
| DOI: | 10.1006/clim.1999.4734 |
| Popis: | A human sequence IgGkappa anti-CD4 monoclonal antibody (mAb), HM6G, originally isolated from a human immunoglobulin transgenic mouse was specific for and bound with high binding avidity to the CD4 antigen expressed on human, chimpanzee, and cynomolgus monkey T cells. Prior to testing this mAb in human clinical trials, a number of preclinical primate studies were performed. In chimpanzees, HM6G did not deplete circulating CD4(+) T cells and was cleared in a dose-dependent manner. In contrast, this mAb administered to cynomolgus monkeys depleted CD4(+) T cells (albeit only at high doses) and its clearance, which had reached saturation even at very low doses, was much slower. These differences were most likely due to the additional and rather substantial expression of the CD4 antigen on chimpanzee monocytes. In monkeys, the T cell depletion was mitigated by infusing the mAb over 30 min or longer (as opposed to 30 s) while only slightly altering the clearance. As expected, the human mAb did not induce an immune response in chimpanzees, although it did induce a low titer response in monkeys. These disparate pharmacokinetic and pharmacodynamic results suggest prudence when extrapolating results obtained in nonhuman models to humans. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect