Transforming preclinical assessment to meet clinical relevance with advanced models

Abstract The advances in the immunotherapy field in the last decade have enabled efficient treatment of previously intractable cancers. These advances have also exposed the limitations of commonly used animal models for safety prediction of such drugs. In fact, 90% biological immunotherapies entering clinical trials fail due to low efficacy and/or unmanageable toxicity despite having undergone rigorous preclinical safety assessment. This low predictability is due to challenges related to the poor conservation of key immune-biological aspects between man and standard preclinical safety workhorses. In order to void this gap new models are urgently needed. Here we discuss the growing area of advanced human physiological in vitro and in silico models and propose future directions needed to enable more accurate and faster prediction of drug responses.