Animal models in preclinical evaluation of CAR-T cell therapy: Advantages and limitations
Abstract
Chimeric Antigen Receptor T (CAR-T) cell therapy is a promising new treatment category. Animal models have played a pivotal role in advancing CAR-T cell therapy. However, no animal model fully replicates human physiology, leading to unsuccessful translation from preclinical models to clinical trials. Understanding the advantages and limitations of various animal model choices requires insight into CAR-T cell mechanisms and their interactions across experimental contexts. CAR-T cell immunobiology differs between animal models and humans. This disparity is reflected in the limited translational capacity of pharmacological parameters and the absence of key immunological interactions in animal models compared to those seen in human trials. Additionally, the antigen specificity of the CAR introduces translational limitations. Differences in antigen density and expression among different cellular populations across species are critical factors to consider when interpreting preclinical results. Xenoreactivity, stemming from the original T-cell receptor repertoire, also limits experimental duration and timing in mouse models. Modeling human cancer in animal models requires many considerations. Cancer heterogeneity varies significantly between patient-derived xenografts and cell-line-based xenografts. Syngeneic models more accurately mimic interactions between CAR-T cells and other immune components, while xenograft models better reflect human tumor antigen expression. Beyond…
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Evidence Hub reads this as a review, done in animal, not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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