An overview of immunotoxicity in drug discovery and development.

The immune system is one of the common targets of drugs' toxicity (Immunotoxicity) and/or efficacy (Immunotherapy). Immunotoxicity leads to adverse effects on human health, which raises serious concerns for the regulatory agencies. Currently, immunotoxicity assessment is conducted using different in vitro and in vivo assays. In silico and in vitro human cell-based immunotoxicity assays should also be explored for screening purposes as these are time and cost effective as well as for ethical reasons. For in vivo studies, tier 1-3 assessments (Tier 1: hematology, serum globulin levels, lymphoid organ's weight and histopathology; Tier 2: immunophenotyping, TDAR and cell mediated immunity; and Tier 3: host resistance) should be used. These non-clinical in vivo assessments are useful to select immunological endpoints for clinical trials as well as for precautionary labeling. As per regulatory guidelines, adverse immunogenicity information of drug should be included in product's labeling to make health care practitioner aware of safety concerns before prescribing medicines and patient management (USFDA, 2022a, 2022b). This review mainly focuses on the importance of immunotoxicity assessment during drug discovery and development.