Introduction to Immunotoxicity
Immunotoxicity refers to adverse effects of exogenous substances on the immune system. Evaluating the potential effects of a drug candidate on immune function is an important component of nonclinical drug development, particularly when conventional toxicity studies indicate changes in immune-related parameters.
Immunotoxic effects can take different forms. Immunosuppression may impair normal immune function and increase susceptibility to infections or potentially affect tumor surveillance. Conversely, excessive or inappropriate immune activation may result in hypersensitivity, autoimmune responses, or other forms of adverse immune stimulation.
When findings from conventional toxicity studies suggest a potential effect on the immune system, additional immunotoxicity studies can be selected based on the nature of the observed changes, the pharmacological properties of the compound, and the intended use of the data. Because the immune system can be sensitive to exogenous substances, targeted assessment may be warranted for compounds with a potential to affect immune function.
Immunotoxicity Studies at Prisys
Prisys Biotechnologies supports preclinical immunotoxicity research using a range of in vitro and in vivo approaches. Depending on the study objectives, species, compound characteristics, and observed findings, the assessment strategy can include conventional toxicity evaluations and additional functional or immunological endpoints.
1. Conventional Toxicity Studies
Conventional toxicity assessments may include:
- Hematology and clinical chemistry
- Gross pathology and organ weight assessment
- Histopathological examination
- Assessment of stress-related changes
- Maximum tolerated dose (MTD) and dose-ranging studies
- Single-dose toxicity studies
- Repeat-dose toxicity studies
- Hypersensitivity studies
- Hemolysis assessment
- Local irritation studies
- In vivo phototoxicity studies
These assessments can provide initial information on systemic toxicity and potential changes affecting the immune system.
2. Additional Immunotoxicity Studies
Where further characterization of immune effects is warranted, additional studies may include:
- Test characterization and assay qualification or verification
- T-cell-dependent antibody response (TDAR)
- Delayed-type hypersensitivity (DTH)
- Immunophenotyping
- Natural killer (NK) cell activity
- Host resistance studies
- Macrophage and neutrophil function
- Cellular immune function assays
The selection of endpoints should be tailored to the suspected mechanism and the specific immunological findings identified during the study.
3. Juvenile Animal Studies
For programs requiring assessment in juvenile animals, potential endpoints may include:
- Physical and sexual development
- Reflex and functional development
- Spontaneous activity
- Learning and memory
- Growth hormone and insulin-like growth factor assessment
- Sperm analysis
- Bone density and bone mass assessment
4. Inhalation Studies
For inhaled drug candidates, immunotoxicity and local tolerability can be evaluated in conjunction with respiratory assessments. Potential endpoints include
