Prediction of CAR-T Therapy In Vitro: Development of Biomimetic Models for CAR-T Killing Effect Assessment.

Chimeric antigen receptor T (CAR-T) cell therapy faces significant challenges in treating solid tumors, particularly due to tumor heterogeneity and the complex tumor microenvironment. These challenges highlight the need for reliable preclinical assessment models. Traditional in vivo models, commonly used for evaluating CAR-T efficacy, often fail to adequately represent the human immune system context. In recent years, various in vitro models have been developed to better simulate the in vivo tumor environment and assess CAR-T cell efficacy. This review summarizes the methodologies commonly employed in the construction of in vitro models, including traditional 2D cell cultures, spheroids, organoids, 3D bioprinting, and tumor-on-a-chip models. Special emphasis is placed on creation of biomimetic tumor microenvironment in the organ-on-a-chip models to evaluate the potency and safety of CAR-T therapy in the context of solid tumors CAR-T treatment.