{"entity":{"id":"idea-in-vivo-car-solid","kind":"idea","name":"In vivo CAR-T against solid-tumour antigens","aka":[],"tldr":"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.","asOf":"2026-09-04","links":[{"label":"Pfeiffer et al., In vivo generation of human CD19-CAR T cells (EMBO Molecular Medicine 2018)","url":"https://doi.org/10.15252/emmm.201809158"}],"tags":[],"related":[],"cancers":["gastric","hcc","pancreatic"],"sections":[],"technologies":["in-vivo-car-t","car-t"],"targets":["cldn18-2","gpc3"],"drugs":["satricabtagene-autoleucel"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-pfeiffer-embo-mol-med","paper-gpc3-hcc-oncoimmunology-2016","paper-cldn18-gastric-front-oncol-2020","paper-gpc3-gastric-pathol-res-pract-2026"],"journals":[],"dependsOn":[],"notes":[],"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.","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"},"route":"/ideas/idea-in-vivo-car-solid/","neighbours":{"cancer":[{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"},{"id":"in-vivo-car-t","kind":"technology","name":"In vivo CAR-T","route":"/technologies/in-vivo-car-t/"}],"target":[{"id":"cldn18-2","kind":"target","name":"Claudin 18.2","route":"/targets/cldn18-2/"},{"id":"gpc3","kind":"target","name":"Glypican-3","route":"/targets/gpc3/"}],"drug":[{"id":"satricabtagene-autoleucel","kind":"drug","name":"Satricabtagene autoleucel","route":"/drugs/satricabtagene-autoleucel/"}],"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-gpc3-hcc-oncoimmunology-2016","kind":"paper","name":"Phase II study of the GPC3-derived peptide vaccine as an adjuvant therapy for hepatocellular carcinoma patients","route":"/key-papers/paper-gpc3-hcc-oncoimmunology-2016/"},{"id":"paper-gpc3-gastric-pathol-res-pract-2026","kind":"paper","name":"Research progress of GPC3 and gastric cancer: Clinicopathologic characteristics and application prospects","route":"/key-papers/paper-gpc3-gastric-pathol-res-pract-2026/"},{"id":"paper-cldn18-gastric-front-oncol-2020","kind":"paper","name":"The Significance of the CLDN18-ARHGAP Fusion Gene in Gastric Cancer: A Systematic Review and Meta-Analysis","route":"/key-papers/paper-cldn18-gastric-front-oncol-2020/"}],"bottleneck":[{"id":"b-manufacturing-cell-therapy","kind":"bottleneck","name":"Manufacturing cost and time for living and radioactive medicines","route":"/bottlenecks/b-manufacturing-cell-therapy/"}],"idea":[{"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/"}]}}