Abstract:
We generated target-humanized mice (e.g., CD5, CD8) for preclinical evaluation of in vivo CAR-T. In CD8-humanized mice, murine CD8 was fully replaced by human CD8 at levels comparable to human PBMC, without impairing immune development or function. Anti-human CD8 tLNPs loaded with reporter mRNA specifically targeted CD8+ T cells in vitro and in vivo, enabling biodistribution visualization. Crossbreeding with CD19/BCMA-humanized mice extends utility for efficacy testing. These models offer a robust platform for assessing in vivo CAR-T delivery, biodistribution, and efficacy.
