ArticleJournal for immunotherapy of cancer2016
Single dose denileukin diftitox does not enhance vaccine-induced T cell responses or effectively deplete Tregs in advanced melanoma: immune monitoring and clinical results of a randomized phase II trial.
Article in Journal for immunotherapy of cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00515528 (Randomized Phase II Study of Multipeptide Vaccination With or Without Regulatory T Cell Depletion Using Ontak in Patients With Metastatic Melanoma), which is not on this map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Randomized Phase II Study of Multipeptide Vaccination With or Without Regulatory T Cell Depletion Using Ontak in Patients With Metastatic Melanoma
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- The soldiers needed to be awakened: Tumor-infiltrating immune cells.Frontiers in genetics · 2022Pooled it
- Neoadjuvant Fc-enhanced anti-CTLA-4 targets Tregs to augment androgen deprivation in high-risk prostate cancer: A randomized phase I trial.Cell reports. Medicine · 2026Trial
- Challenges and Future Perspectives for Vaccines Targeting the Tumor Microenvironment.Vaccines · 2026Article
- Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026Review
- Targeting regulatory T cells in gastrointestinal cancers: current status and future perspectives.International journal of clinical oncology · 2026Review
- Durable response to an anti-CD25 antibody-drug conjugate and anti-PD-1 antibody in ovarian carcinoma: a case report.Immunotherapy · 2025Article
- Regulatory T cell and endothelial cell crosstalk.Nature reviews. Immunology · 2025Review
- Approaches for Increasing Cerebral Efflux of Amyloid-β in Experimental Systems.Journal of Alzheimer's disease : JAD · 2024Review
- Implications of regulatory T cells in anti-cancer immunity: from pathogenesis to therapeutics.Heliyon · 2022Review
- Mechanisms of regulatory T cell infiltration in tumors: implications for innovative immune precision therapies.Journal for immunotherapy of cancer · 2021Review
- The Therapeutic Potential of Regulatory T Cells: Challenges and Opportunities.Frontiers in immunology · 2020Review
- Regulatory T Cells in Cancer Immunotherapy: Basic Research Outcomes and Clinical Directions.Cancer management and research · 2020Review
- Review
- Depletion of regulatory T cells in tumors with an anti-CD25 immunotoxin induces CD8 T cell-mediated systemic antitumor immunity.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Tumor Tolerance-Promoting Function of Regulatory T Cells Is Optimized by CD28, but Strictly Dependent on Calcineurin.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Combination Immunotherapy: Taking Cancer Vaccines to the Next Level.Frontiers in immunology · 2018Review
- Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundDepletion of CD25(+) Tregs improves anti-tumor immunity in preclinical models. Denileukin diftitox is a recombinant fusion protein of human IL-2 and diptheria toxin fragment that also can kill CD25(+) T cells. Prior clinical trials of denileukin diftitox suggested reduction of FoxP3(+) Tregs and some clinical responses.
methodTo investigate the immunologic effects of denileukin difitox on vaccine-specific immune responses in melanoma, a randomized clinical trial of single dose denileukin diftitox prior to vaccination versus vaccination alone in subjects with HLA-A2(+) metastatic melanoma was performed. Treatment included randomization to a 4-peptide vaccine (Melan-A, gp100, MAGE3 and NA17 with GM-CSF emulsified in Montanide) alone or after single dose of denileukin diftitox (18 mcg/kg). Vaccine was given every 2 weeks for 3 doses and, absent clinical progression, continued every 2 weeks. Blood and tumor biopsies were obtained pretreatment and after 3 vaccinations for immunologic assessments.
resultsIn 17 treated subjects there were no drug-related G3-4 adverse events. One partial response and 8 stable disease were observed in 9 subjects (4 DD: 5 vaccine only) with no impact of denileukin diftitox on time to progression. Total peripheral Tregs were not significantly altered, and in 1 patient biopsy intra-tumoral FoxP3 transcripts were not reduced following denileukin diftitox. ELISA for IL2R-α demonstrated no impact on outcomes by soluble CD25 level. Immune monitoring suggested the development of modest vaccine-specific CD8(+) T cell responses in the control group, however immunization efficacy was actually reduced in the denileukin diftitox group.
conclusionOur results indicate that denileukin diftitox did not effectively deplete Tregs, augment T cell responses, or improve clinical activity in melanoma. Clinicaltrials.gov ID: NCT00515528; Registered August 9, 2007.
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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.