{"entity":{"id":"paper-besser-til-melanoma-intent-to-treat-ccr-2013","kind":"paper","name":"Adoptive transfer of tumor-infiltrating lymphocytes in patients with metastatic melanoma: intent-to-treat analysis and efficacy after failure to prior immunotherapies","aka":[],"tldr":"Sheba's decade of growing melanoma patients' own tumour-fighting cells and giving them back, reported honestly: counting everyone who enrolled, not only those who made it to treatment.","summary":"The Ella Lemelbaum Institute at Sheba Medical Center began treating metastatic melanoma with autologous tumour-infiltrating lymphocytes in 2006, more than a decade before any regulator approved the approach. This report is the intent-to-treat analysis of the first 80 patients with stage IV disease enrolled in the programme.\n\nTumour-infiltrating lymphocyte cultures could be established for 72 of the 80. Fifty-seven were treated with unselected or young lymphocytes and high-dose interleukin-2 after non-myeloablative lymphodepleting conditioning. Twenty-three were withdrawn, mostly because they deteriorated clinically during the weeks the cells were being grown, which is the cost of a manufacturing step that cannot be hurried.\n\nThe overall response rate was 29 percent and median survival 9.8 months counting everyone enrolled; 40 percent and 15.2 months counting those actually treated. Five patients achieved complete and 18 partial remission. Every complete responder remained in unmaintained remission at a median follow-up of 28 months, and three-year survival among responders was 78 percent. On multivariate analysis, lactate dehydrogenase, sex, days of culture and the total number of infused CD8-positive cells independently predicted outcome. Thirty-two patients received ipilimumab before or after the cells; patients who had not responded to ipilimumab or interleukin-2 did about as well on cell therapy as those who had.","asOf":"2026-09-25","links":[{"label":"Clin Cancer Res 2013","url":"https://doi.org/10.1158/1078-0432.ccr-13-0380"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/23690483/"}],"tags":[],"related":[],"cancers":["melanoma"],"sections":["cell-therapy"],"technologies":["til-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":["sheba"],"pathways":[],"terms":[],"trials":[],"people":["michal-besser","jacob-schachter","gal-markel"],"bottlenecks":["b-manufacturing-cell-therapy"],"keyPapers":[],"journals":["clinical-cancer-research"],"dependsOn":[],"notes":[],"journal":"Clinical Cancer Research","year":2013,"doi":"10.1158/1078-0432.ccr-13-0380","pmid":"23690483","authors":"Besser MJ, Shapira-Frommer R, Itzhaki O, Treves AJ, Zippel DB, Levy D, Kubi A, Shoshani N, Zikich D, Ohayon Y, Ohayon D, Shalmon B, Markel G, Yerushalmi R, Apter S, Ben-Nun A, Schachter J, et al.","paperType":"observational","findings":["Cultures established for 72 of 80 enrolled patients; 57 treated; 23 withdrawn, mainly through clinical deterioration during manufacture.","Overall response rate 29 percent and median survival 9.8 months on intent to treat; 40 percent and 15.2 months among treated patients.","Five complete and 18 partial remissions; all complete responders in unmaintained remission at a median 28 months; three-year survival among responders 78 percent.","Lactate dehydrogenase, sex, days of cells in culture and total infused CD8-positive cells were independent predictors of outcome.","Failure of prior ipilimumab or interleukin-2 did not predict failure of cell therapy."],"whatItMeans":"It showed that a single academic centre outside the United States could run tumour-infiltrating lymphocyte therapy at scale and get durable remissions, and it quantified the attrition that intent-to-treat reporting exposes and single-arm treated-patient reporting hides.","caveats":["Single-arm, single-centre and not randomised, in an era before checkpoint inhibitors became standard first-line treatment, so the comparison group is historical.","High-dose interleukin-2 and lymphodepletion make the regimen unsuitable for frail patients, and the three-week manufacturing window excluded nearly a third of those enrolled."],"participants":80},"route":"/key-papers/paper-besser-til-melanoma-intent-to-treat-ccr-2013/","neighbours":{"cancer":[{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"}],"section":[{"id":"cell-therapy","kind":"section","name":"Cell Therapy","route":"/fronts/cell-therapy/"}],"technology":[{"id":"til-therapy","kind":"technology","name":"TIL therapy","route":"/technologies/til-therapy/"}],"institution":[{"id":"sheba","kind":"institution","name":"Sheba Medical Center","route":"/institutions/sheba/"}],"person":[{"id":"gal-markel","kind":"person","name":"Gal Markel","route":"/people/gal-markel/"},{"id":"jacob-schachter","kind":"person","name":"Jacob Schachter","route":"/people/jacob-schachter/"},{"id":"michal-besser","kind":"person","name":"Michal Besser","route":"/people/michal-besser/"}],"bottleneck":[{"id":"b-manufacturing-cell-therapy","kind":"bottleneck","name":"Manufacturing cost and time for living and radioactive medicines","route":"/bottlenecks/b-manufacturing-cell-therapy/"}],"journal":[{"id":"clinical-cancer-research","kind":"journal","name":"Clinical Cancer Research","route":"/journals/clinical-cancer-research/"}]}}