Trained Immunity: RoadMap for drug discovery and development.

Trained Immunity is the nonspecific (pathogen agnostic) memory of innate immune cells, characterized by altered responses upon secondary stimulation. This review provides a RoadMap for the discovery and development of therapeutics targeting Trained Immunity, aimed at researchers with strong scientific backgrounds but limited drug development experience. The article outlines five drug development domains - epigenetic, metabolic, differentiation, inflammatory, and memory changes - that guide the identification of molecular targets, model selection, and biomarker development for the discovery and development of Trained Immunity-based therapeutics. It emphasizes the application of preclinical models and artificial intelligence in target discovery and compound screening. Additionally, the review addresses challenges in translating preclinical Trained Immunity findings to clinical trials and highlights relevant disease indications and ongoing clinical trials. This review integrates scientific findings with development strategy and thereby aims to bridge the gap between discovery and clinical application, advancing the field of Trained Immunity-based therapeutics.