Robust In Vivo CAR-T Efficacy Evaluation in a PBMC-Reconstituted NCG-MHC-dKO Model with Delayed GvHD

Humanized mouse models are widely used for evaluating CAR-T therapies, yet rapid onset of graft-versus-host disease (GvHD) severely restricts long-term studies. GemPharmatech developed a PBMC-reconstituted NCG-MHC-dKO mouse model with significantly delayed GvHD, extending the therapeutic window. In this model, Nalm-6 tumors were engrafted and treated with in vivo CAR-T generation using either lentiviral vectors or lipid nanoparticle (LNP)-delivered CD19-targeting constructs. Tumor burden was monitored by bioluminescence imaging. Both approaches successfully generated functional CAR-T cells in vivo, resulting potent tumor growth inhibition and prolonged survival. This improved model provides a robust and durable platform for comparative assessment of CAR-T therapies.