{"entity":{"id":"paper-wallen-fludarabine-ctl-melanoma-plos-one-2009","kind":"paper","name":"Fludarabine modulates immune response and extends in vivo survival of adoptively transferred CD8 T cells in patients with metastatic melanoma","aka":[],"tldr":"A small trial in ten people with advanced melanoma that compared how long infused T cells lasted with and without the chemotherapy drug fludarabine first. Fludarabine made them last about three times longer.","summary":"In a first-in-human phase I study (FHCRC 1796, NCT00317759), patients with refractory metastatic melanoma received two infusions of a single tumour-reactive antigen-specific CTL clone, the first without and the second after fludarabine 25 mg/m2 a day for five days, allowing an intra-patient comparison (PLoS ONE 2009). Nineteen infusions were given to ten patients with no serious toxicities (PLoS ONE 2009).","asOf":"2026-11-05","links":[{"label":"DOI 10.1371/journal.pone.0004749","url":"https://doi.org/10.1371/journal.pone.0004749"},{"label":"PubMed 19270751","url":"https://pubmed.ncbi.nlm.nih.gov/19270751/"},{"label":"ClinicalTrials.gov NCT00317759","url":"https://clinicaltrials.gov/study/NCT00317759"}],"tags":[],"related":[],"cancers":["melanoma"],"sections":[],"technologies":[],"targets":[],"drugs":["fludarabine"],"companies":[],"institutions":["fred-hutch"],"pathways":[],"terms":["endogenous-t-cell-therapy","lymphodepletion"],"trials":["nct00317759"],"people":["cassian-yee"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo agent (Claude Opus 5.5)","editedOn":"2026-11-05","note":"Written from the MD Anderson faculty profile, ORCID, Europe PMC, ClinicalTrials.gov v2, SEC EDGAR and each organisation's own site, read on 5 November 2026."},"journal":"PLoS ONE","year":2009,"doi":"10.1371/journal.pone.0004749","pmid":"19270751","authors":"Wallen H, Thompson JA, Reilly JZ, Rodmyre RM, Cao J, Yee C.","paperType":"translational","findings":["Fludarabine improved in vivo persistence of transferred CTL clones 2.9-fold, from a median of 4.5 days (range 0 to 38+) to 13.0 days (range 2 to 63+) (p<0.05).","Three of nine evaluable patients had minor response or stable disease for 5.8 to 11.0 months; median overall survival was 9.7 months.","Fludarabine raised plasma IL-7 and IL-15 and also raised the share of CD4+ T cells expressing Foxp3."],"whatItMeans":"Lymphodepletion before infusion helps transferred T cells survive, but the rise in regulatory T cells suggests conditioning alone is not enough for anti-tumour effect.","caveats":["Ten patients, phase I; the authors conclude that further improvements to T-cell survival and to regulatory T cells are needed."],"participants":10},"route":"/key-papers/paper-wallen-fludarabine-ctl-melanoma-plos-one-2009/","neighbours":{"cancer":[{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"}],"drug":[{"id":"fludarabine","kind":"drug","name":"Fludarabine","route":"/drugs/fludarabine/"}],"institution":[{"id":"fred-hutch","kind":"institution","name":"Fred Hutchinson Cancer Center","route":"/institutions/fred-hutch/"}],"term":[{"id":"endogenous-t-cell-therapy","kind":"term","name":"Endogenous T-cell therapy","route":"/terms/endogenous-t-cell-therapy/"},{"id":"lymphodepletion","kind":"term","name":"Lymphodepletion before CAR-T","route":"/terms/lymphodepletion/"}],"trial":[{"id":"nct00317759","kind":"trial","name":"Fludarabine before CD8+ antigen-specific T-cell clones in stage IV melanoma (Fred Hutchinson phase 1)","route":"/trials/nct00317759/"}],"person":[{"id":"cassian-yee","kind":"person","name":"Cassian Yee","route":"/people/cassian-yee/"}]}}