# In vivo CAR-T

Source: https://onco.cc/technologies/in-vivo-car-t/  
OnCo record `in-vivo-car-t` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Technology
- Status: phase-1
- Last checked: 2026-09-04
- Tags: frontier
- Principle: CD8- or CD3-targeted LNP or viral vector transduces circulating T cells to express a CAR in situ.
- Since: 2024
- Strengths: Off-the-shelf, redosable, no lymphodepletion; Potentially 10x cheaper
- Limitations: Transduction efficiency and durability; Off-target transfection; Very early

## Sources

- 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): https://doi.org/10.15252/emmm.201809158

## Connected records

- fronts: [Cell Therapy](https://onco.cc/fronts/cell-therapy/)
- technologies: [CAR-T cell therapy](https://onco.cc/technologies/car-t/), [Closed automated cell-therapy manufacturing](https://onco.cc/technologies/closed-automated-cell-manufacturing/), [Engineered exosomes as drug carriers](https://onco.cc/technologies/exosome-therapeutics/), [In vivo base and prime editing for cancer](https://onco.cc/technologies/in-vivo-gene-editing-cancer/), [Logic-gated therapeutics (AND, NOT gates)](https://onco.cc/technologies/logic-gated-therapeutics/), [Self-amplifying and circular RNA therapeutics](https://onco.cc/technologies/self-amplifying-rna/)
- companies: [AbbVie (incl. ImmunoGen, Capstan)](https://onco.cc/companies/abbvie/), [Adicet Bio](https://onco.cc/companies/adicet-bio/), [Capstan Therapeutics](https://onco.cc/companies/capstan-therapeutics/), [Interius BioTherapeutics](https://onco.cc/companies/interius/), [Kelonia Therapeutics](https://onco.cc/companies/kelonia-therapeutics/), [Kernal Biologics](https://onco.cc/companies/kernal-biologics/), [Orna Therapeutics (Eli Lilly)](https://onco.cc/companies/orna-therapeutics/), [Sana Biotechnology](https://onco.cc/companies/sana-biotechnology/), [Strand Therapeutics](https://onco.cc/companies/strand-therapeutics/), [TScan Therapeutics](https://onco.cc/companies/tscan/), [Umoja Biopharma](https://onco.cc/companies/umoja-biopharma/)
- key papers: [In vivo generation of human CD19-CAR T cells results in B-cell depletion and signs of cytokine release syndrome](https://onco.cc/key-papers/paper-pfeiffer-embo-mol-med/), [UCART19: the first gene-edited, donor-derived CAR-T cells in children and adults with relapsed B-cell ALL](https://onco.cc/key-papers/paper-ucart19-allogeneic-car-t-lancet-2020/)
- cancers: [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/)
- institutions: [Abramson Cancer Center, University of Pennsylvania](https://onco.cc/institutions/penn-abramson/)
- roadmaps: [Cell therapy roadmap: CD19 CAR-T → solid tumours → in vivo CAR](https://onco.cc/roadmaps/cell-therapy-roadmap/), [Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity](https://onco.cc/roadmaps/immunotherapy-roadmap/)
- ideas: [In vivo CAR-T against solid-tumour antigens](https://onco.cc/ideas/idea-in-vivo-car-solid/), [In vivo CAR-T as a vial on the shelf: a cost and access trial in lymphoma](https://onco.cc/ideas/idea-reg-in-vivo-cart-off-the-shelf-vial/), [In vivo CAR-T manufactured and priced like a generic biologic](https://onco.cc/ideas/idea-moon-in-vivo-cart-generic-price/)
- people: [Bruce L. Levine](https://onco.cc/people/bruce-levine/), [Christof von Kalle](https://onco.cc/people/christof-von-kalle/), [Drew Weissman](https://onco.cc/people/drew-weissman/), [Hans-Peter Kiem](https://onco.cc/people/hans-peter-kiem/), [Michel Sadelain](https://onco.cc/people/michel-sadelain/)
- bottlenecks: [Manufacturing cost and time for living and radioactive medicines](https://onco.cc/bottlenecks/b-manufacturing-cell-therapy/)
- terms: [Lymphodepletion before CAR-T](https://onco.cc/terms/lymphodepletion/)

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