{"entity":{"id":"logic-gated-therapeutics","kind":"technology","name":"Logic-gated therapeutics (AND, NOT gates)","aka":[],"tldr":"Cells or drugs that fire only when two conditions are true at once, so healthy tissue expressing just one of them is spared.","summary":"SynNotch and similar circuits require antigen A to license killing of antigen B; NOT gates use an inhibitory receptor against an antigen present only on normal tissue. Tmod NOT-gated CAR-T exploiting HLA loss of heterozygosity is in early-phase trials, and AND-gated constructs are in phase 1 for solid tumours. Logic gating is the leading answer to on-target off-tumour toxicity, but circuit complexity reduces potency and manufacturability.","status":"phase-1","asOf":"2026-09-08","links":[{"label":"ClinicalTrials.gov: logic-gated CAR T","url":"https://clinicaltrials.gov/search?term=logic%20gated%20CAR%20T"}],"tags":["frontier","promising"],"related":[],"cancers":[],"sections":["cell-therapy","targeted-therapy"],"technologies":["car-t","armored-car","masked-adc","bispecific-adc","in-vivo-car-t"],"targets":[],"drugs":[],"companies":["arsenal-bio","sana-biotechnology"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"A synthetic receptor circuit integrates two antigen inputs; killing proceeds only if the required combination is present, and is blocked if a protective antigen is detected.","strengths":["Directly addresses the antigen-specificity ceiling in solid tumours","Turns non-specific antigens into usable targets","Applies to bispecifics and masked drugs as well as cells"],"limitations":["Complex constructs are harder to manufacture and less potent","Antigen loss defeats AND gates","Very early clinical data"]},"route":"/technologies/logic-gated-therapeutics/","neighbours":{"section":[{"id":"cell-therapy","kind":"section","name":"Cell Therapy","route":"/fronts/cell-therapy/"},{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"technology":[{"id":"armored-car","kind":"technology","name":"Armoured, logic-gated & next-gen CARs","route":"/technologies/armored-car/"},{"id":"bispecific-adc","kind":"technology","name":"Bispecific ADC","route":"/technologies/bispecific-adc/"},{"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":"masked-adc","kind":"technology","name":"Masked / conditionally active ADC","route":"/technologies/masked-adc/"}],"company":[{"id":"arsenal-bio","kind":"company","name":"Arsenal Biosciences","route":"/companies/arsenal-bio/"},{"id":"sana-biotechnology","kind":"company","name":"Sana Biotechnology","route":"/companies/sana-biotechnology/"}],"roadmap":[{"id":"cure-paths","kind":"roadmap","name":"Paths to cures: interception, eradication, control","route":"/roadmaps/cure-paths/"},{"id":"frontier-2035","kind":"roadmap","name":"Radical oncology: what could change the war by 2035","route":"/roadmaps/frontier-2035/"}],"term":[{"id":"antigen-escape","kind":"term","name":"Antigen escape (antigen loss, lineage switch)","route":"/terms/antigen-escape/"}]}}