Instead of engineering T cells in a factory, an injection reprograms them inside the patient's body.
Targeted lipid nanoparticles (Capstan/AbbVie CPTX2309, Orna) or lentiviral vectors (Umoja, Interius INT2104) deliver CAR-encoding mRNA or DNA to T cells in vivo. First-in-human data (2025-26) show B-cell depletion and responses without lymphodepletion or manufacturing wait. Transient mRNA expression may reduce long-term risk. Capstan was acquired by AbbVie for up to $2.1B in 2025, signalling the field's expectations.
CD8- or CD3-targeted LNP or viral vector transduces circulating T cells to express a CAR in situ.
The UCART19 report was the first clinical evidence that a universal, pre-manufactured CAR-T made from a donor can work, avoiding the weeks of autologous manufacturing and the problem of patients whose own T cells are too damaged. It set the template for later allogeneic programmes (including cemacabtagene autoleucel in the ALPHA studies) and for in vivo CAR generation. Short persistence and the need for deep lymphodepletion remain the central weaknesses.
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