Trial reportJournal of immunology (Baltimore, Md. : 1950)2007
Administration of a CD25-directed immunotoxin, LMB-2, to patients with metastatic melanoma induces a selective partial reduction in regulatory T cells in vivo.
Trial report in Journal of immunology (Baltimore, Md. : 1950), 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
84 citing papers in PubMed, 164 citations in OpenAlex.
- Trial
- Partial reduction of human FOXP3+ CD4 T cells in vivo after CD25-directed recombinant immunotoxin administration.Journal of immunotherapy (Hagerstown, Md. : 1997)Trial
- Microenvironmental regulation of solid tumour resistance to CAR T cell therapy.Nature reviews. Immunology · 2026Review
- Anti-HER2×CCR4 bispecific antibody enhances antitumor immunity in advanced HER2-positive tumors by chemotaxis blockade and depletion of tumor-associated Tregs, without inducing systemic toxicity.Journal for immunotherapy of cancer · 2025Article
- USP7 at the Crossroads of Ubiquitin Signaling, Cell Cycle, and Tumorigenesis.Molecules (Basel, Switzerland) · 2025Review
- CD70 as a target in cancer immunotherapy: advances, challenges, and future directions.Frontiers in oncology · 2025Review
- Quantitative Approach to Explore Regulatory T Cell Activity in Immuno-Oncology.Pharmaceutics · 2024Review
- Antisense targeting of FOXP3+ Tregs to boost anti-tumor immunity.Frontiers in immunology · 2024Article
- Drug conjugates for targeting regulatory T cells in the tumor microenvironment: guided missiles for cancer treatment.Experimental & molecular medicine · 2023Review
- The protective role of the microenvironment in hairy cell leukemia treatment: Facts and perspectives.Frontiers in oncology · 2023Review
- Managing the TME to improve the efficacy of cancer therapy.Frontiers in immunology · 2022Review
- Bacteria-derived chimeric toxins as potential anticancer agents.Frontiers in oncology · 2022Review
- Retargeting IL-2 Signaling to NKG2D-Expressing Tumor-Infiltrating Leukocytes Improves Adoptive Transfer Immunotherapy.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- A Novel CAR Expressing NK Cell Targeting CD25 With the Prospect of Overcoming Immune Escape Mechanism in Cancers.Frontiers in oncology · 2021Article
- Blocking inflammation to improve immunotherapy of advanced cancer.Immunology · 2020Review
- Regulatory T Cells in Cancer Immunotherapy: Basic Research Outcomes and Clinical Directions.Cancer management and research · 2020Review
- Immunogenicity of Immunotoxins ContainingFrontiers in immunology · 2020Review
- Recent advances with Treg depleting fusion protein toxins for cancer immunotherapy.Immunotherapy · 2019Review
- 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
- Pharmacokinetics of protein and peptide conjugates.Drug metabolism and pharmacokinetics · 2019Review
24 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 1 institution in 1 country.
Funding
Abstract
CD25+ CD4+ T regulatory (Treg) cells regulate peripheral self tolerance and possess the ability to suppress antitumor responses, which may in part explain the poor clinical response of cancer patients undergoing active immunization protocols. We have previously shown that in vitro incubation of human PBMC with LMB-2, a CD25-directed immunotoxin, significantly reduced CD25+ FOXP3+ CD4+ Treg cells without impairing the function of the remaining lymphocytes. In the current study, eight patients with metastatic melanoma were treated with LMB-2 followed by MART-1 and gp100-specific peptide vaccination. LMB-2 administration resulted in a preferential, transient reduction in mean circulating CD25+ CD4+ T cell number, from 83 +/- 16 cells/microl to a nadir of 17 +/- 5 cells/microl, a 79.1% reduction. FOXP3 analysis revealed a less robust depletion with mean FOXP3+ CD4+ Treg cell number decreasing from 74 +/- 15 cells/microl to 36 +/- 8 cells/microl, a 51.4% reduction. FOXP3+ CD4+ Treg cells that survived LMB-2-mediated cytotoxicity expressed little or no CD25. Similar to the peripheral blood, immunohistochemical analysis showed a 68.9% mean reduction in FOXP3+ CD4+ Treg cell frequency in evaluable lesions. Despite inducing a reduction in Treg cell numbers in vivo, LMB-2 therapy did not augment the immune response to cancer vaccination and no patient experienced an objective response or autoimmunity. These data demonstrate the capacity of a CD25-directed immunotoxin to selectively mediate a transient partial reduction in circulating and tumor-infiltrating Treg cells in vivo, and suggest that more comprehensive Treg cell elimination may be required to bolster antitumor responses in patients with metastatic melanoma.
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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.