{"entity":{"id":"idea-moon-engineered-immune-surveillance","kind":"idea","name":"Engineered immune surveillance: long-lived programmed immune cells that patrol for early cancer","aka":[],"tldr":"For people at very high cancer risk, install a small population of engineered immune cells that live for years and destroy cells showing early cancer signals before a tumour forms.","summary":"Immune surveillance normally eliminates most incipient tumours; carriers of BRCA, Lynch or TP53 mutations and people with clonal haematopoiesis face lifelong high risk. Advances in memory stem T cell engineering, logic-gated receptors responsive to stress ligands or shared neoantigens, and safety switches make a persistent, low-level engineered surveillance population conceivable. The proposal is a research programme to define target ligands of pre-malignant cells, engineer persistent gated cells with off-switches, and demonstrate prevention in genetically engineered mouse models before first-in-human studies in the highest-risk carriers.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (Dormant cells and minimal residual disease): Tie et al., ctDNA analysis guiding adjuvant therapy in stage II colon cancer (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2200075"}],"tags":[],"related":[],"cancers":[],"sections":[],"technologies":["car-t","tcr-t","car-nk-macrophage","armored-car"],"targets":["tp53","brca"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":["b-dormancy-mrd","b-hereditary-risk","b-tme-immunosuppression"],"keyPapers":["paper-vogelstein-surfing-p53-network-nature-2000"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"Engineered surveillance cells reduce tumour incidence by more than half in high-risk mouse models without autoimmunity, and persist for over a year in humans with an acceptable safety profile.","rationale":"Cell therapies persist for years in some patients; logic gating and stress-ligand recognition have preclinical proof; prevention needs far fewer cells than treating bulk disease.","test":"Five-year preclinical programme with a go/no-go on incidence reduction and safety in two mouse models, then a phase 1 in Li-Fraumeni or Lynch carriers with persistence and safety endpoints.","maturity":"speculative","actor":"research","cost":"large","horizonYears":12},"route":"/ideas/idea-moon-engineered-immune-surveillance/","neighbours":{"technology":[{"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":"tcr-t","kind":"technology","name":"TCR-T cell therapy","route":"/technologies/tcr-t/"}],"target":[{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"bottleneck":[{"id":"b-tme-immunosuppression","kind":"bottleneck","name":"Cold tumours and the immunosuppressive microenvironment","route":"/bottlenecks/b-tme-immunosuppression/"},{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"},{"id":"b-hereditary-risk","kind":"bottleneck","name":"Inherited risk is mostly unidentified","route":"/bottlenecks/b-hereditary-risk/"}],"paper":[{"id":"paper-vogelstein-surfing-p53-network-nature-2000","kind":"paper","name":"Vogelstein, Lane and Levine 2000: surfing the p53 network","route":"/key-papers/paper-vogelstein-surfing-p53-network-nature-2000/"}]}}