Evidence map›Paper›PMID 18481388›Full record

Trial reportJournal of immunotherapy (Hagerstown, Md. : 1997)

Partial reduction of human FOXP3+ CD4 T cells in vivo after CD25-directed recombinant immunotoxin administration.

Daniel J Powell, Peter Attia, Victor Ghetie, John Schindler, Ellen S Vitetta, Steven A Rosenberg

Abstract readClinical Trial
In one paragraph

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 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 10% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Article
  5. Article
  6. Review
  7. T-Regulatory Cells In Tumor Progression And Therapy.Cancer management and research · 2019
    Review
  8. Regulatory T cells in the immunotherapy of melanoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Immunotherapy for ovarian cancer: what's next?Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2011
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Daniel J PowellSurgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. poda@mail.med.upenn.edu
Peter Attia
Victor Ghetie
John Schindler
Ellen S Vitetta
Steven A Rosenberg
The University of Texas Southwestern Medical Center · USNational Cancer Institute · USNational Institutes of Health · US

Funding

Adoptive Cell Transfer Immunotherapy of CancerZIABC010984 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ROSENBERG, STEVEN · 2009 to 2025
$56.8M
SURGICAL CONSULTATIONS AND COLLABORATIVE RESEARCH IN SURGICAL SERVICES AT NIHZ01SC003800 · SC · DIVISION OF CLINICAL SCIENCES - NCI · PI ROSENBERG, STEVEN A · 1996 to 2008
$7.5M
THE IMMUNOTHERAPY OF ANIMAL AND HUMAN CANCERZ01SC003811 · SC · CLINICAL SCIENCES · PI ROSENBERG, STEVEN A · 1996 to 2007
$3.2M
Gene therapy of cancerZ01BC010985 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ROSENBERG, STEVEN · 2008 to 2008
$1.5M
Intramural NIH HHS Z01 SC003811
6 · The paper itself

Abstract

The regulation of tolerance to self-proteins and the suppression of T-cell responses have in part been attributed to the activity of CD25+CD4+ T regulatory (Treg) cells. Further, Treg cells can inhibit the antitumor effectiveness of adoptive immunotherapy and active immunization approaches in preclinical models. In an effort to selectively eliminate Treg cells from human peripheral blood mononuclear cell to potentially bolster antitumor responses, we have evaluated the Treg-cell depleting capacity of the CD25-directed immunotoxin, RFT5-SMPT-dgA. In preclinical studies, incubation of human peripheral blood mononuclear cell with RFT5-SMPT-dgA mediated a partial reduction in the levels of CD25+, Foxp3-expressing CD4+ T cells in vitro. Administration of RFT5-SMPT-dgA to 6 patients with metastatic melanoma induced a transient but robust reduction in the number of CD25high CD4 T cells in vivo (a 97.5% mean reduction at nadir; from 69.4 +/- 12.4 cells/miroL to 1.7 +/- 0.3 cells/microL). The reduction in FOXP3+ CD4 T-cell number was less comprehensive (a 71.3% mean reduction at nadir; from 66.6 +/- 16.5 cells/microL to 14.2 +/- 3.9 cells/tL). This resulted in the selective persistence of a stable number of CD25(low/neg) FOXP3+ CD4+ T cells in vivo. No objective antitumor responses were seen in any patient. Our results indicate that the CD25-directed, RFT5-SMPT-dgA immunotoxin can mediate a transient, partial reduction in Treg-cell frequency and number in vitro and in vivo and suggest that comprehensive eradication of human Treg cells in vivo may require the ability to target and eliminate FOXP3+ CD4+ T cells expressing both high and low levels of CD25.

Indexed as

AdultAntibodiesAntibodies, MonoclonalCD4 Lymphocyte CountCD8-Positive T-LymphocytesCell CountFemaleForkhead Transcription FactorsHumansImmunoconjugatesImmunotherapyInterleukin-2 Receptor alpha SubunitLeukocytes, MononuclearLymphocyte CountLymphocyte DepletionMaleAntibodiesAntibodies, MonoclonalForkhead Transcription FactorsFOXP3 protein, humanImmunoconjugatesInterleukin-2 Receptor alpha SubunitRFT5-SMPT-dgA immunotoxinRicin

Identifiers

PMID18481388
PMCPMC3480218
OpenAlexW1978382182

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.