{"id":"cell-therapy-roadmap","name":"Cell therapy roadmap: CD19 CAR-T → solid tumours → in vivo CAR","route":"/roadmaps/cell-therapy-roadmap/","eras":[{"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).","status":"historic","refs":[{"id":"til-therapy","kind":"technology","name":"TIL therapy","route":"/technologies/til-therapy/","status":"approved","tldr":"Immune cells that have already found their way into the tumour are harvested, grown to billions, and returned."}],"trials":[],"papers":[]},{"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.","status":"historic","refs":[{"id":"axicabtagene-ciloleucel","kind":"drug","name":"Axicabtagene ciloleucel","route":"/drugs/axicabtagene-ciloleucel/","status":"approved","tldr":"A CD19 CAR-T that cures about 40% of patients with large B-cell lymphoma who had failed everything, and beat transplant in second line."},{"id":"ciltacabtagene-autoleucel","kind":"drug","name":"Ciltacabtagene autoleucel","route":"/drugs/ciltacabtagene-autoleucel/","status":"approved","tldr":"Ciltacabtagene autoleucel is a one-time BCMA CAR-T for myeloma that, in CARTITUDE-4, cut the risk of death by about 45% compared with standard regimens."},{"id":"blinatumomab","kind":"drug","name":"Blinatumomab","route":"/drugs/blinatumomab/","status":"approved","tldr":"Blinatumomab was the first T-cell engager (2014), and is now given to children and adults with leukaemia even when in remission, because it improves survival."},{"id":"teclistamab","kind":"drug","name":"Teclistamab","route":"/drugs/teclistamab/","status":"approved","tldr":"Teclistamab was the first off-the-shelf bispecific for multiple myeloma, and is now approved after just one prior line of therapy."}],"trials":[],"papers":[]},{"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.","status":"current","refs":[{"id":"lifileucel","kind":"drug","name":"Lifileucel","route":"/drugs/lifileucel/","status":"approved","tldr":"Lifileucel was the first approved TIL therapy: the patient's own tumour-fighting immune cells are expanded to billions and given back."},{"id":"afamitresgene-autoleucel","kind":"drug","name":"Afamitresgene autoleucel","route":"/drugs/afamitresgene-autoleucel/","status":"approved","tldr":"Afamitresgene autoleucel was the first engineered T-cell receptor therapy approved for a solid tumour, synovial sarcoma."},{"id":"satricabtagene-autoleucel","kind":"drug","name":"Satricabtagene autoleucel","route":"/drugs/satricabtagene-autoleucel/","status":"approved","tldr":"Satricabtagene autoleucel (satri-cel) is the first CAR-T therapy approved for a solid tumour (gastric cancer), in China."},{"id":"cldn18-2","kind":"target","name":"Claudin 18.2","route":"/targets/cldn18-2/","tldr":"A tight-junction protein normally hidden in the stomach lining that becomes exposed in gastric and pancreatic cancers."},{"id":"gpc3","kind":"target","name":"Glypican-3","route":"/targets/gpc3/","tldr":"Glypican-3 is a fetal liver protein that reappears in liver cancer, giving CAR-T and bispecifics a clean target."},{"id":"mage-a4","kind":"target","name":"MAGE-A4","route":"/targets/mage-a4/","tldr":"A protein normally only in testis that some sarcomas and other tumours switch on; T cells can be engineered to recognise fragments of it."}],"trials":[],"papers":[]},{"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.","status":"emerging","refs":[{"id":"in-vivo-car-t","kind":"technology","name":"In vivo CAR-T","route":"/technologies/in-vivo-car-t/","status":"phase-1","tldr":"Instead of engineering T cells in a factory, an injection reprograms them inside the patient's body."},{"id":"allogeneic-cell-therapy","kind":"technology","name":"Allogeneic (off-the-shelf) cell therapy","route":"/technologies/allogeneic-cell-therapy/","status":"phase-2","tldr":"Cell therapies made from healthy donors in advance, so patients do not have to wait for their own cells to be engineered."},{"id":"car-nk-macrophage","kind":"technology","name":"CAR-NK & CAR-macrophage","route":"/technologies/car-nk-macrophage/","status":"phase-1","tldr":"Putting the cancer-seeking receptor on natural killer cells or macrophages instead of T cells, which could be safer and off-the-shelf."},{"id":"abbvie","kind":"company","name":"AbbVie (incl. ImmunoGen, Capstan)","route":"/companies/abbvie/","tldr":"AbbVie owns Venclexta and Elahere, and bought Capstan, the leading in vivo CAR-T company."}],"trials":[],"papers":[]},{"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.","status":"speculative","refs":[{"id":"armored-car","kind":"technology","name":"Armoured, logic-gated & next-gen CARs","route":"/technologies/armored-car/","status":"phase-1","tldr":"Upgraded CAR-T cells that also secrete immune boosters, resist exhaustion, or only fire when two signals are present."},{"id":"tcr-t","kind":"technology","name":"TCR-T cell therapy","route":"/technologies/tcr-t/","status":"approved","tldr":"T cells engineered with a receptor that sees fragments of proteins inside the cancer cell, reaching targets CAR-T cannot."},{"id":"fap","kind":"target","name":"FAP","route":"/targets/fap/","tldr":"FAP (fibroblast activation protein) sits on the cancer-associated fibroblasts that scaffold more than 90% of epithelial cancers and is almost absent from normal adult tissue. FAPI PET tracers therefore light up tumours with high contrast, including pancreatic, gastric and low-grade cancers where FDG PET is weak, and FAP-targeted radioligands are in development."}],"trials":[],"papers":[]}],"watch":[]}