# Fludarabine modulates immune response and extends in vivo survival of adoptively transferred CD8 T cells in patients with metastatic melanoma

Source: https://onco.cc/key-papers/paper-wallen-fludarabine-ctl-melanoma-plos-one-2009/  
OnCo record `paper-wallen-fludarabine-ctl-melanoma-plos-one-2009` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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).

## Fields

- Kind: Key paper
- Last checked: 2026-11-05
- Journal: PLoS ONE
- Year: 2009
- DOI: 10.1371/journal.pone.0004749
- Authors: Wallen H, Thompson JA, Reilly JZ, Rodmyre RM, Cao J, Yee C.
- 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.
- What it means: 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.

## Sources

- DOI 10.1371/journal.pone.0004749: https://doi.org/10.1371/journal.pone.0004749
- PubMed 19270751: https://pubmed.ncbi.nlm.nih.gov/19270751/
- ClinicalTrials.gov NCT00317759: https://clinicaltrials.gov/study/NCT00317759

## Connected records

- cancers: [Melanoma](https://onco.cc/cancers/melanoma/)
- drugs: [Fludarabine](https://onco.cc/drugs/fludarabine/)
- institutions: [Fred Hutchinson Cancer Center](https://onco.cc/institutions/fred-hutch/)
- terms: [Endogenous T-cell therapy](https://onco.cc/terms/endogenous-t-cell-therapy/), [Lymphodepletion before CAR-T](https://onco.cc/terms/lymphodepletion/)
- trials: [Fludarabine before CD8+ antigen-specific T-cell clones in stage IV melanoma (Fred Hutchinson phase 1)](https://onco.cc/trials/nct00317759/)
- people: [Cassian Yee](https://onco.cc/people/cassian-yee/)

---
JSON: https://onco.cc/api/v1/entities/paper-wallen-fludarabine-ctl-melanoma-plos-one-2009.json