Trial reportJournal of translational medicine2008
Transient T cell depletion causes regression of melanoma metastases.
Trial report in Journal of translational medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00299689 (Phase II Trial of ONTAK With Metastatic Melanoma), which is not on this map. Cited by 69 papers.
What it found
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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.
Phase II Trial of ONTAK With Metastatic Melanoma
Who cites it
69 citing papers in PubMed, 163 citations in OpenAlex.
- 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
- Foxp3(+) cell infiltration and granzyme B(+)/Foxp3(+) cell ratio are associated with outcome in neoadjuvant chemotherapy-treated ovarian carcinoma.Cancer immunology, immunotherapy : CII · 2010Trial
- Review
- Regulatory T cells in liver metastases: emerging and divergent roles in tumour progression.eGastroenterology · 2025Review
- Causal association between skin cancer and immune cells: mendelian randomization (MR) study.BMC cancer · 2024Article
- Th17/Treg cell balance in patients with papillary thyroid carcinoma: a new potential biomarker and therapeutic target.Frontiers in oncology · 2024Review
- Targeting regulatory T cells by E7777 enhances CD8 T-cell-mediated anti-tumor activity and extends survival benefit of anti-PD-1 in solid tumor models.Frontiers in immunology · 2023Article
- Distinct genomic features across cytolytic subgroups in skin melanoma.Cancer immunology, immunotherapy : CII · 2021Article
- Metabolic profiles of regulatory T cells in the tumour microenvironment.Cancer immunology, immunotherapy : CII · 2021Review
- Understanding and Targeting Human Cancer Regulatory T Cells to Improve Therapy.Advances in experimental medicine and biology · 2021Article
- A Novel CAR Expressing NK Cell Targeting CD25 With the Prospect of Overcoming Immune Escape Mechanism in Cancers.Frontiers in oncology · 2021Article
- Overcoming Immune Evasion in Melanoma.International journal of molecular sciences · 2020Review
- Local and systemic immunosuppression in pancreatic cancer: Targeting the stalwarts in tumor's arsenal.Biochimica et biophysica acta. Reviews on cancer · 2020Review
- Recent advances with Treg depleting fusion protein toxins for cancer immunotherapy.Immunotherapy · 2019Review
- Analysis of Treg/Th17 cells in patients with tongue squamous cell carcinoma.Experimental and therapeutic medicine · 2019Article
- Review
- Review
- Second-generation IL-2 receptor-targeted diphtheria fusion toxin exhibits antitumor activity and synergy with anti-PD-1 in melanoma.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Combination Immunotherapy: Taking Cancer Vaccines to the Next Level.Frontiers in immunology · 2018Review
9 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
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCognate immunity against neoplastic cells depends on a balance between effector T cells and regulatory T (Treg) cells. Treg cells prevent immune attack against normal and neoplastic cells by directly suppressing the activation of effector CD4+ and CD8+ T cells. We postulated that a recombinant interleukin 2/diphtheria toxin conjugate (DAB/IL2; Denileukin Diftitox; Ontak) may serve as a useful strategy to deplete Treg cells and break tolerance against neoplastic tumors in humans.
methodsWe administered DAB/IL2 (12 microg/kg; four daily doses; 21 day cycles) to 16 patients with metastatic melanoma and measured the effects on the peripheral blood concentration of several T cell subsets and on tumor burden.
resultsWe found that DAB/IL2 caused a transient depletion of Treg cells as well as total CD4+ and CD8+ T cells (< 21 days). T cell repopulation coincided with the de novo appearance of melanoma antigen-specific CD8+ T cells in several patients as determined by flow cytometry using tetrameric MART-1, tyrosinase and gp100 peptide/MHC conjugates. Sixteen patients received at least one cycle of DAB/IL2 and five of these patients experienced regressions of melanoma metastases as measured by CT and/or PET imaging. One patient experienced a near complete response with the regression of several hepatic and pulmonary metastases coupled to the de novo appearance of MART-1-specific CD8+ T cells. A single metastatic tumor remained in this patient and, after surgical resection, immunohistochemical analysis revealed MART1+ melanoma cells surrounded by CD8+ T cells.
conclusionTaken together, these data indicate that transient depletion of T cells in cancer patients may disrupt the homeostatic control of cognate immunity and allow for the expansion of effector T cells with specificity against neoplastic cells. Several T cell depleting agents are clinically available and this study provides strong rationale for an examination of their efficacy in cancer patients.
trial registrationNCT00299689 (ClinicalTrials.gov Identifier).
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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.