{"entity":{"id":"cell-therapy-roadmap","kind":"roadmap","name":"Cell therapy roadmap: CD19 CAR-T → solid tumours → in vivo CAR","aka":[],"tldr":"From a cure for some leukaemias in 2017 to the first solid-tumour CAR-T and the prospect of making CAR-T inside the body with an injection.","summary":"This roadmap starts with the foundations of cell therapy, Rosenberg's TIL therapy in melanoma and the first-generation CARs, then the approvals of CD19 and BCMA CAR-T alongside T-cell engagers as off-the-shelf competitors. Blood cancers were the easy case with a clean antigen and accessible cells; the current step brings solid tumours within reach through lifileucel, afamitresgene autoleucel and CLDN18.2, GD2 and GPC3 CAR-T. The emerging manufacturing revolution covers gene-edited allogeneic products and in vivo CAR-T made inside the body by targeted LNPs or lentivirus, ending speculatively with in vivo CAR as an outpatient injection. The route links CAR-T, TIL, TCR-T, in vivo CAR-T, allogeneic cell therapy and CAR-NK, and is pointed to by glioblastoma and the manufacturing bottleneck.","asOf":"2026-09-04","links":[{"label":"ELIANA: the global trial that made tisagenlecleucel the first approved CAR-T therapy for children and young adults with relapsed ALL (New England Journal of Medicine 2018)","url":"https://doi.org/10.1056/NEJMoa1709866"},{"label":"CARTITUDE-4: cilta-cel CAR-T versus standard combinations after one to three prior lines of myeloma therapy (New England Journal of Medicine 2023)","url":"https://doi.org/10.1056/NEJMoa2303379"}],"tags":[],"related":[],"cancers":[],"sections":["cell-therapy"],"technologies":["car-t","til-therapy","tcr-t","in-vivo-car-t","allogeneic-cell-therapy","armored-car","car-nk-macrophage"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"steps":[{"era":"1988-2016","title":"Foundations","description":"Rosenberg's TIL therapy in melanoma (1988); first-generation CARs (Eshhar, 1989); 4-1BB and CD28 costimulation (June, Sadelain, Campana); Emily Whitehead treated with CTL019 (2012).","refs":["til-therapy"],"status":"historic"},{"era":"2017-2022","title":"CD19 and BCMA CAR-T approved","description":"Tisagenlecleucel and axicabtagene (2017), then five more products; ZUMA-7 puts CAR-T ahead of transplant in second-line lymphoma; ide-cel and cilta-cel in myeloma; blinatumomab and teclistamab establish off-the-shelf T-cell engagers as competitors.","refs":["axicabtagene-ciloleucel","ciltacabtagene-autoleucel","blinatumomab","teclistamab"],"status":"historic"},{"era":"2024-2026","title":"Solid tumours: TIL, TCR-T, CAR-T","description":"Solid-tumour cell therapy arrives: lifileucel (melanoma TIL, 2024), afamitresgene autoleucel (MAGE-A4 TCR-T, synovial sarcoma, 2024; age ≥12 in 2026), satri-cel (CLDN18.2 CAR-T, gastric, China 2025), GD2 CAR-T in neuroblastoma and glioma, GPC3 CAR-T in HCC. CAR-T expands to autoimmune disease.","refs":["lifileucel","afamitresgene-autoleucel","satricabtagene-autoleucel","cldn18-2","gpc3","mage-a4"],"status":"current"},{"era":"2025-2028","title":"Manufacturing revolution: allogeneic and in vivo","description":"Gene-edited allogeneic products (cema-cel, ALLO-316) show feasibility with persistence limits. In vivo CAR-T via targeted LNPs (Capstan/AbbVie, Orna) and lentivirus (Umoja, Interius) enter first-in-human trials with B-cell depletion and no lymphodepletion. iPSC-derived CAR-NK. CAR-T cost and access become policy issues.","refs":["in-vivo-car-t","allogeneic-cell-therapy","car-nk-macrophage","abbvie"],"status":"emerging"},{"era":"2028+","title":"Speculative","description":"Logic-gated and armoured CARs for solid tumours; neoantigen-specific TCR-T at scale via AI-predicted TCRs; in vivo CAR as an outpatient injection for lymphoma and autoimmune disease; CAR-T against fibroblast and myeloid targets; regional delivery for glioma, mesothelioma, and pancreatic cancer.","refs":["armored-car","tcr-t","fap"],"status":"speculative"}],"watch":[]},"route":"/roadmaps/cell-therapy-roadmap/","neighbours":{"section":[{"id":"cell-therapy","kind":"section","name":"Cell Therapy","route":"/fronts/cell-therapy/"}],"technology":[{"id":"allogeneic-cell-therapy","kind":"technology","name":"Allogeneic (off-the-shelf) cell therapy","route":"/technologies/allogeneic-cell-therapy/"},{"id":"armored-car","kind":"technology","name":"Armoured, logic-gated & next-gen CARs","route":"/technologies/armored-car/"},{"id":"car-nk-macrophage","kind":"technology","name":"CAR-NK & CAR-macrophage","route":"/technologies/car-nk-macrophage/"},{"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/"},{"id":"tcr-t","kind":"technology","name":"TCR-T cell therapy","route":"/technologies/tcr-t/"},{"id":"til-therapy","kind":"technology","name":"TIL therapy","route":"/technologies/til-therapy/"}],"drug":[{"id":"afamitresgene-autoleucel","kind":"drug","name":"Afamitresgene autoleucel","route":"/drugs/afamitresgene-autoleucel/"},{"id":"axicabtagene-ciloleucel","kind":"drug","name":"Axicabtagene ciloleucel","route":"/drugs/axicabtagene-ciloleucel/"},{"id":"blinatumomab","kind":"drug","name":"Blinatumomab","route":"/drugs/blinatumomab/"},{"id":"ciltacabtagene-autoleucel","kind":"drug","name":"Ciltacabtagene autoleucel","route":"/drugs/ciltacabtagene-autoleucel/"},{"id":"lifileucel","kind":"drug","name":"Lifileucel","route":"/drugs/lifileucel/"},{"id":"satricabtagene-autoleucel","kind":"drug","name":"Satricabtagene autoleucel","route":"/drugs/satricabtagene-autoleucel/"},{"id":"teclistamab","kind":"drug","name":"Teclistamab","route":"/drugs/teclistamab/"}],"target":[{"id":"cldn18-2","kind":"target","name":"Claudin 18.2","route":"/targets/cldn18-2/"},{"id":"fap","kind":"target","name":"FAP","route":"/targets/fap/"},{"id":"gpc3","kind":"target","name":"Glypican-3","route":"/targets/gpc3/"},{"id":"mage-a4","kind":"target","name":"MAGE-A4","route":"/targets/mage-a4/"}],"company":[{"id":"abbvie","kind":"company","name":"AbbVie (incl. ImmunoGen, Capstan)","route":"/companies/abbvie/"}],"cancer":[{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"}],"bottleneck":[{"id":"b-manufacturing-cell-therapy","kind":"bottleneck","name":"Manufacturing cost and time for living and radioactive medicines","route":"/bottlenecks/b-manufacturing-cell-therapy/"}],"roadmap":[{"id":"paediatric-oncology-roadmap","kind":"roadmap","name":"Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first","route":"/roadmaps/paediatric-oncology-roadmap/"}]}}