{"entity":{"id":"in-vivo-car-t","kind":"technology","name":"In vivo CAR-T","aka":[],"tldr":"Instead of engineering T cells in a factory, an injection reprograms them inside the patient's body.","summary":"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.","status":"phase-1","asOf":"2026-09-04","links":[{"label":"Pfeiffer et al., In vivo generation of human CD19-CAR T cells results in B-cell depletion and signs of cytokine release syndrome (EMBO Molecular Medicine 2018)","url":"https://doi.org/10.15252/emmm.201809158"}],"tags":["frontier"],"related":[],"cancers":[],"sections":["cell-therapy"],"technologies":["car-t"],"targets":[],"drugs":[],"companies":["abbvie","adicet-bio","capstan-therapeutics","kelonia-therapeutics","kernal-biologics","strand-therapeutics"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-pfeiffer-embo-mol-med"],"journals":[],"dependsOn":[],"notes":[],"principle":"CD8- or CD3-targeted LNP or viral vector transduces circulating T cells to express a CAR in situ.","strengths":["Off-the-shelf, redosable, no lymphodepletion","Potentially 10x cheaper"],"limitations":["Transduction efficiency and durability","Off-target transfection","Very early"],"since":2024},"route":"/technologies/in-vivo-car-t/","neighbours":{"section":[{"id":"cell-therapy","kind":"section","name":"Cell Therapy","route":"/fronts/cell-therapy/"}],"technology":[{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"},{"id":"closed-automated-cell-manufacturing","kind":"technology","name":"Closed automated cell-therapy manufacturing","route":"/technologies/closed-automated-cell-manufacturing/"},{"id":"exosome-therapeutics","kind":"technology","name":"Engineered exosomes as drug carriers","route":"/technologies/exosome-therapeutics/"},{"id":"in-vivo-gene-editing-cancer","kind":"technology","name":"In vivo base and prime editing for cancer","route":"/technologies/in-vivo-gene-editing-cancer/"},{"id":"logic-gated-therapeutics","kind":"technology","name":"Logic-gated therapeutics (AND, NOT gates)","route":"/technologies/logic-gated-therapeutics/"},{"id":"self-amplifying-rna","kind":"technology","name":"Self-amplifying and circular RNA therapeutics","route":"/technologies/self-amplifying-rna/"}],"company":[{"id":"abbvie","kind":"company","name":"AbbVie (incl. ImmunoGen, Capstan)","route":"/companies/abbvie/"},{"id":"adicet-bio","kind":"company","name":"Adicet Bio","route":"/companies/adicet-bio/"},{"id":"capstan-therapeutics","kind":"company","name":"Capstan Therapeutics","route":"/companies/capstan-therapeutics/"},{"id":"interius","kind":"company","name":"Interius BioTherapeutics","route":"/companies/interius/"},{"id":"kelonia-therapeutics","kind":"company","name":"Kelonia Therapeutics","route":"/companies/kelonia-therapeutics/"},{"id":"kernal-biologics","kind":"company","name":"Kernal Biologics","route":"/companies/kernal-biologics/"},{"id":"orna-therapeutics","kind":"company","name":"Orna Therapeutics (Eli Lilly)","route":"/companies/orna-therapeutics/"},{"id":"sana-biotechnology","kind":"company","name":"Sana Biotechnology","route":"/companies/sana-biotechnology/"},{"id":"strand-therapeutics","kind":"company","name":"Strand Therapeutics","route":"/companies/strand-therapeutics/"},{"id":"tscan","kind":"company","name":"TScan Therapeutics","route":"/companies/tscan/"},{"id":"umoja-biopharma","kind":"company","name":"Umoja Biopharma","route":"/companies/umoja-biopharma/"}],"paper":[{"id":"paper-pfeiffer-embo-mol-med","kind":"paper","name":"In vivo generation of human CD19-CAR T cells results in B-cell depletion and signs of cytokine release syndrome","route":"/key-papers/paper-pfeiffer-embo-mol-med/"},{"id":"paper-ucart19-allogeneic-car-t-lancet-2020","kind":"paper","name":"UCART19: the first gene-edited, donor-derived CAR-T cells in children and adults with relapsed B-cell ALL","route":"/key-papers/paper-ucart19-allogeneic-car-t-lancet-2020/"}],"cancer":[{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"}],"institution":[{"id":"penn-abramson","kind":"institution","name":"Abramson Cancer Center, University of Pennsylvania","route":"/institutions/penn-abramson/"}],"roadmap":[{"id":"cell-therapy-roadmap","kind":"roadmap","name":"Cell therapy roadmap: CD19 CAR-T → solid tumours → in vivo CAR","route":"/roadmaps/cell-therapy-roadmap/"},{"id":"immunotherapy-roadmap","kind":"roadmap","name":"Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity","route":"/roadmaps/immunotherapy-roadmap/"}],"idea":[{"id":"idea-in-vivo-car-solid","kind":"idea","name":"In vivo CAR-T against solid-tumour antigens","route":"/ideas/idea-in-vivo-car-solid/"},{"id":"idea-reg-in-vivo-cart-off-the-shelf-vial","kind":"idea","name":"In vivo CAR-T as a vial on the shelf: a cost and access trial in lymphoma","route":"/ideas/idea-reg-in-vivo-cart-off-the-shelf-vial/"},{"id":"idea-moon-in-vivo-cart-generic-price","kind":"idea","name":"In vivo CAR-T manufactured and priced like a generic biologic","route":"/ideas/idea-moon-in-vivo-cart-generic-price/"}],"person":[{"id":"bruce-levine","kind":"person","name":"Bruce L. Levine","route":"/people/bruce-levine/"},{"id":"christof-von-kalle","kind":"person","name":"Christof von Kalle","route":"/people/christof-von-kalle/"},{"id":"drew-weissman","kind":"person","name":"Drew Weissman","route":"/people/drew-weissman/"},{"id":"hans-peter-kiem","kind":"person","name":"Hans-Peter Kiem","route":"/people/hans-peter-kiem/"},{"id":"michel-sadelain","kind":"person","name":"Michel Sadelain","route":"/people/michel-sadelain/"}],"bottleneck":[{"id":"b-manufacturing-cell-therapy","kind":"bottleneck","name":"Manufacturing cost and time for living and radioactive medicines","route":"/bottlenecks/b-manufacturing-cell-therapy/"}],"term":[{"id":"lymphodepletion","kind":"term","name":"Lymphodepletion before CAR-T","route":"/terms/lymphodepletion/"}]}}