# In vivo CAR-T against solid-tumour antigens

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

## TL;DR

If a lipid nanoparticle can make CAR-T cells inside the body for lymphoma, it could be redosed weekly against solid-tumour targets that autologous CAR-T cannot sustain.

## Summary

If a lipid nanoparticle can make CAR-T cells inside the body for lymphoma, this idea redoses it weekly against Claudin 18.2 and Glypican-3 in gastric, liver and pancreatic cancer. Solid-tumour CAR-T fails partly through exhaustion and poor persistence of a single infused product, whereas transient, redosable in vivo CAR expression could deliver repeated waves of fresh effector cells, limit off-tumour toxicity, avoid lymphodepletion and remove manufacturing delay. The test is a phase 1 in CLDN18.2-positive gastric cancer after the satricabtagene autoleucel proof of concept, measuring CAR-positive T-cell frequency, tumour infiltration and toxicity per dose. Speculative in maturity, it addresses the bottleneck Manufacturing cost and time for living and radioactive medicines.

## Fields

- Kind: Idea
- Last checked: 2026-09-04
- Hypothesis: Weekly in vivo CAR mRNA-LNP against CLDN18.2 or GPC3 produces response rates comparable to ex vivo CAR-T with lower toxicity and no manufacturing delay.
- Rationale: Transient expression limits on-target off-tumour toxicity; repeated dosing avoids exhaustion of a single product; no lymphodepletion needed.
- Proposed test: Phase 1 in CLDN18.2+ gastric cancer after satri-cel proof of concept; measure CAR+ T-cell frequency, tumour infiltration, and toxicity per dose.
- Maturity: speculative

## Sources

- Pfeiffer et al., In vivo generation of human CD19-CAR T cells (EMBO Molecular Medicine 2018): https://doi.org/10.15252/emmm.201809158

## Connected records

- cancers: [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [CAR-T cell therapy](https://onco.cc/technologies/car-t/), [In vivo CAR-T](https://onco.cc/technologies/in-vivo-car-t/)
- targets: [Claudin 18.2](https://onco.cc/targets/cldn18-2/), [Glypican-3](https://onco.cc/targets/gpc3/)
- drugs: [Satricabtagene autoleucel](https://onco.cc/drugs/satricabtagene-autoleucel/)
- 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/), [Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients](https://onco.cc/key-papers/paper-gpc3-hcc-oncoimmunology-2016/), [Research progress of GPC3 and gastric cancer: Clinicopathologic characteristics and application prospects](https://onco.cc/key-papers/paper-gpc3-gastric-pathol-res-pract-2026/), [The Significance of the CLDN18-ARHGAP Fusion Gene in Gastric Cancer: A Systematic Review and Meta-Analysis](https://onco.cc/key-papers/paper-cldn18-gastric-front-oncol-2020/)
- bottlenecks: [Manufacturing cost and time for living and radioactive medicines](https://onco.cc/bottlenecks/b-manufacturing-cell-therapy/)
- ideas: [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/)

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