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In Vivo Generation of CAR-T Cells: Current Obstacles, Strategic Solutions, and Clinical Translation - PubMed

2 hours ago
  • #clinical translation
  • #in vivo generation
  • #CAR-T therapy
  • Chimeric antigen receptor T (CAR-T) cell therapy is a breakthrough for hematologic malignancies, but traditional ex vivo manufacturing is expensive, time-consuming, and not easily scalable.
  • In vivo generation of CAR-T cells, where endogenous T cells are reprogrammed directly inside patients using engineered vectors, presents a simpler and more accessible option.
  • Key challenges include inefficient systemic delivery, off-target transduction, balancing transfection efficiency with safety, and short-lived CAR expression.
  • Innovative strategies like targeted vector systems, combinatorial T-cell recognition, tunable expression control, and methods to boost durability are being developed.
  • Early-phase clinical trials confirm that inducing CAR-T cells in vivo is feasible, paving the way for future translation of this therapy.