Preclinical Safety Assessment of 2 Inhaled Single-Domain Antibodies in the Cynomolgus Monkey
| Autor: | Molly H. Boyle, Richard Haworth, George Karantabias, Reenu Gupta, Paul Edwards, Rajni Fagg, Mark Price |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Pathology
medicine.medical_specialty Necrosis Tracheobronchial lymph nodes Inhalation Toxicology Toxicology Peripheral blood mononuclear cell Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Administration Inhalation medicine Animals Lung Molecular Biology Lymph node 030304 developmental biology 0303 health sciences medicine.diagnostic_test Inhalation business.industry Cell Biology Single-Domain Antibodies Macaca fascicularis medicine.anatomical_structure Bronchoalveolar lavage medicine.symptom business Bronchoalveolar Lavage Fluid 030215 immunology |
| Zdroj: | Toxicologic Pathology. 49:296-314 |
| ISSN: | 1533-1601 0192-6233 |
| DOI: | 10.1177/0192623320972387 |
| Popis: | The safety of 2 single domain antibodies (dAbs) was evaluated by inhalation toxicology studies in the cynomolgus monkey. In the first case study, a 14-day repeat-dose study evaluating an anti-thymic stromal lymphopoietin (anti-TSLP) dAb resulted in minimal mononuclear inflammatory cell infiltrates in the lungs, increases in lymphocytes in bronchoalveolar lavage fluid, and development of antidrug antibodies (ADAs). In a 6-week inhalation study, there was an increase in incidence and/or severity of mononuclear cell infiltrates in the lung, increased cellularity in the tracheobronchial lymph node (TBLN), and development of ADA. The second case study evaluated a change in duration of inhalation dosing, a different route of exposure (intravenous or IV), and recovery following an off-dose period with an anti-tumor necrosis factor receptor 1 dAb. A 7-day repeat-dose inhalation study and a 14-day IV study produced no microscopic effects in the lung, whereas a 14-day inhalation study resulted in moderate increases in pulmonary perivascular/peribronchiolar/alveolar lymphocytic infiltrates and increased cellularity in the TBLN, with partial and full recovery, respectively, after 14 days. The lung and lymph node findings seen after inhalation of either dAb were considered secondary to the immunogenic response to a human protein and were considered nonadverse. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|