{"entity":{"id":"idea-bio2-til-reactivity-selection","kind":"idea","name":"Select patients for cell therapy by whether their tumour holds reactive T cells","aka":[],"tldr":"Growing a patient's own tumour-fighting cells only works if those cells are there to start with. A test for them would spare futile treatment.","summary":"Tumour-infiltrating lymphocyte therapy is approved in melanoma but works in a minority, and manufacturing takes weeks and costs a great deal. Markers of genuinely tumour-reactive T cells, notably CD39 and CD69 co-expression and CXCL13 expression, distinguish reactive from bystander cells in human tumours. A pre-manufacture biopsy assay could predict product potency and patient benefit.","asOf":"2026-09-08","links":[{"label":"Bottleneck evidence (No one can predict who responds to immunotherapy): Haslam & Prasad (JAMA Network Open 2019)","url":"https://doi.org/10.1001/jamanetworkopen.2019.2535"}],"tags":[],"related":[],"cancers":["melanoma","nsclc"],"sections":[],"technologies":["til-therapy","single-cell-spatial","flow-cytometry-mrd"],"targets":[],"drugs":["lifileucel"],"companies":["iovance"],"institutions":[],"pathways":[],"terms":["tils"],"trials":[],"people":["john-haanen","ton-schumacher"],"bottlenecks":["b-immunotherapy-response","b-manufacturing-cell-therapy","b-biomarker-validation"],"keyPapers":["paper-haslam-jama-netw-open"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"A pre-manufacture reactivity assay predicts objective response to tumour-infiltrating lymphocyte therapy, allowing at least a third of patients unlikely to benefit to avoid a costly and toxic procedure.","rationale":"Bystander T cells dominate many tumours, so total lymphocyte density is a poor proxy for reactivity. Product potency assays are standard in cell therapy manufacture in other diseases, and the markers here are well characterised in human tissue.","test":"Retrospective analysis of banked pre-manufacture biopsies from treated patients for association with response; if positive, use the assay prospectively as an eligibility criterion in one arm of a trial.","maturity":"preclinical-evidence","actor":"industry","cost":"medium","horizonYears":5},"route":"/ideas/idea-bio2-til-reactivity-selection/","neighbours":{"cancer":[{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"technology":[{"id":"flow-cytometry-mrd","kind":"technology","name":"Multiparameter flow cytometry MRD","route":"/technologies/flow-cytometry-mrd/"},{"id":"single-cell-spatial","kind":"technology","name":"Single-cell & spatial profiling","route":"/technologies/single-cell-spatial/"},{"id":"til-therapy","kind":"technology","name":"TIL therapy","route":"/technologies/til-therapy/"}],"drug":[{"id":"lifileucel","kind":"drug","name":"Lifileucel","route":"/drugs/lifileucel/"}],"company":[{"id":"iovance","kind":"company","name":"Iovance Biotherapeutics","route":"/companies/iovance/"}],"term":[{"id":"tils","kind":"term","name":"Tumour-infiltrating lymphocytes (TILs)","route":"/terms/tils/"}],"person":[{"id":"john-haanen","kind":"person","name":"John Haanen","route":"/people/john-haanen/"},{"id":"ton-schumacher","kind":"person","name":"Ton Schumacher","route":"/people/ton-schumacher/"}],"bottleneck":[{"id":"b-biomarker-validation","kind":"bottleneck","name":"Biomarkers are not validated or standardised","route":"/bottlenecks/b-biomarker-validation/"},{"id":"b-manufacturing-cell-therapy","kind":"bottleneck","name":"Manufacturing cost and time for living and radioactive medicines","route":"/bottlenecks/b-manufacturing-cell-therapy/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}],"paper":[{"id":"paper-haslam-jama-netw-open","kind":"paper","name":"Estimation of the Percentage of US Patients With Cancer Who Are Eligible for and Respond to Checkpoint Inhibitor Immunotherapy Drugs","route":"/key-papers/paper-haslam-jama-netw-open/"}]}}