Novel modalities biologics such as CAR T and gene therapy have shown remarkable clinical efficacy and are in development for multiple indications. The complexity of these modalities, as well as the multiple ways they can interact with the human immune system, can make preclinical immunogenicity risk assessment and mitigation challenging. Immunogenicity risk assessment tools developed for biologics (mAbs) can be adapted to evaluate and assess immunogenicity risk of novel modalities biologics.