Trial reportJournal of immunotherapy (Hagerstown, Md. : 1997)
Inability of a fusion protein of IL-2 and diphtheria toxin (Denileukin Diftitox, DAB389IL-2, ONTAK) to eliminate regulatory T lymphocytes in patients with melanoma.
Trial report in Journal of immunotherapy (Hagerstown, Md. : 1997). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
110 citing papers in PubMed, 2 syntheses or guidelines pooled it, 290 citations in OpenAlex.
- Meta-Analysis of Interleukin-2 Receptor Antagonists as the Treatment for Steroid-Refractory Acute Graft-Frontiers in immunology · 2021Pooled it
- Clinical outcomes of active specific immunotherapy in advanced colorectal cancer and suspected minimal residual colorectal cancer: a meta-analysis and system review.Journal of translational medicine · 2011Pooled it
- Trial
- Phase II trial of the regulatory T cell-depleting agent, denileukin diftitox, in patients with unresectable stage IV melanoma.BMC cancer · 2011Trial
- Immunotherapy of malignant melanoma with tumor lysate-pulsed autologous monocyte-derived dendritic cells.Yonsei medical journal · 2011Trial
- Trial
- Transient T cell depletion causes regression of melanoma metastases.Journal of translational medicine · 2008Trial
- Administration of a CD25-directed immunotoxin, LMB-2, to patients with metastatic melanoma induces a selective partial reduction in regulatory T cells in vivo.Journal of immunology (Baltimore, Md. : 1950) · 2007Trial
- Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients.Cancer immunology, immunotherapy : CII · 2007Trial
- Partial reduction of human FOXP3+ CD4 T cells in vivo after CD25-directed recombinant immunotoxin administration.Journal of immunotherapy (Hagerstown, Md. : 1997)Trial
- Review
- Regulatory T cells in the tumour microenvironment.Nature reviews. Cancer · 2025Review
- Nanoparticle Therapeutics in Clinical Perspective: Classification, Marketed Products, and Regulatory Landscape.Small (Weinheim an der Bergstrasse, Germany) · 2025Review
- A Phase II Study of Denileukin Diftitox in Patients with Advanced Treatment Refractory Breast Cancer.Vaccines · 2025Article
- Development and Characterization of an Anti-PD-L1 Immunotoxin for Targeted Cancer Therapy.Current pharmaceutical biotechnology · 2025Article
- Antisense targeting of FOXP3+ Tregs to boost anti-tumor immunity.Frontiers in immunology · 2024Article
- Targeting tumor-infiltrating tregs for improved antitumor responses.Frontiers in immunology · 2024Review
- Acquisition of suppressive function by conventional T cells limits antitumor immunity upon TScience immunology · 2023Article
- A deubiquitination module essential for TScience advances · 2022Article
- Therapeutic targeting of regulatory T cells in cancer.Trends in cancer · 2022Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Elimination of regulatory T lymphocytes may provide a way to break self-tolerance and unleash the anti-tumor properties of circulating lymphocytes. The use of fusion proteins, which link cytotoxic molecules to receptor targets, provides one approach to this problem. This study examined the ability of a fusion protein of interleukin-2 (IL-2) and diphtheria toxin (Denileukin Diftitox, DAB389IL-2, ONTAK) to eliminate regulatory T lymphocytes based on their expression of high-affinity IL-2 receptors. Thirteen patients (12 with metastatic melanoma, 1 with metastatic renal cell carcinoma) were treated at one of the two Food and Drug Administration-approved doses of Denileukin Diftitox (seven patients at 9 microg/kg, six patients at 18 microg/kg). None of the patients experienced an objective clinical response. Foxp3 expression did not decrease significantly overall, although it did decrease minimally among patients receiving 18 microg/kg (-2.01+/-0.618 copies of Foxp3/10(3) copies of beta-actin; P=0.031). Denileukin Diftitox did not decrease the suppressive ability of CD4CD25 cells as quantified by an in vitro co-culture suppression assay. Furthermore, the increased numbers of lymphocytes in patients resulting from treatment with IL-2 were not susceptible to Denileukin Diftitox. Administration of Denileukin Diftitox does not appear to eliminate regulatory T lymphocytes or cause regression of metastatic melanoma.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.