Evidence map›Paper›PMID 20824708›Full record

ArticleInternational journal of cancer2011

Affinity-matured anti-glycoprotein NMB recombinant immunotoxins targeting malignant gliomas and melanomas.

Chien-Tsun Kuan, Kenji Wakiya, Stephen T Keir, Jianjun Li, James E Herndon, Ira Pastan, Darell D Bigner

Open access · bronzeAbstract read
In one paragraph

Article in International journal of cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.5field-weighted citation impact, top 12% 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

19 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Synthesis of an Anti-CD7 Recombinant Immunotoxin Based on PE24 in CHO andInternational journal of molecular sciences · 2022
    Article
  3. Article
  4. Glycoprotein nonmetastatic melanoma protein B accelerates tumorigenesis of cervical cancer in vitro by regulating the Wnt/β-catenin pathway.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2018
    Article
  5. Review
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  12. Review
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  14. Article
  15. Article
  16. Toxin-based targeted therapy for malignant brain tumors.Clinical & developmental immunology · 2012
    Review
  17. Review
  18. Article
  19. 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

7 authors at 3 institutions in 1 country.

Chien-Tsun KuanPreston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA. kuan@duke.edu
Kenji Wakiya
Stephen T Keir
Jianjun Li
James E Herndon
Ira Pastan
Darell D Bigner
Duke Medical Center · USDuke University Hospital · USNational Institutes of Health · US

Funding

Immunotoxin Therapy of Solid and Hematopoietic Tumors: Preclinical StudiesZIABC008753 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI PASTAN, IRA · 2009 to 2024
$33.1M
TUMOR SUPPRESSOR GENES IN HUMAN MEDULLOBLASTOMAP50NS020023 · NINDS · DUKE UNIVERSITY · PI BIGNER, DARELL D · 1985 to 2013
$17.3M
TEMODAR RESISTANCE IN CENTRAL NERVOUS SYSTEMP50CA108786 · NCI · DUKE UNIVERSITY · PI BIGNER, DARELL D · 2004 to 2009
$12.3M
BRAIN TUMORS: IMMUNOLOGICAL AND BIOLOGICAL STUDIESR37CA011898 · NCI · DUKE UNIVERSITY · PI BIGNER, DARELL D · 1988 to 2012
$8.1M
CSF DEFICIENCY AND ANTITUMOR IMMUNITYR01CA074886 · NCI · DANA-FARBER CANCER INSTITUTE · PI DRANOFF, GLENN · 1997 to 2004
$1.3M
Intramural NIH HHSNCI NIH HHS CA 5P50 108786NCI NIH HHS P50 CA108786NCI NIH HHS R01 CA074886NCI NIH HHS R37 CA011898NCRR NIH HHS MO1 RR30NINDS NIH HHS 5P50 NS020023NINDS NIH HHS P50 NS020023
6 · The paper itself

Abstract

Glycoprotein NMB (GPNMB), a transmembrane glycoprotein highly expressed in high-grade gliomas (HGGs), is an attractive target in cancer immunotherapy. We isolated a GPNMB-specific scFv clone, G49, from a human synthetic phage-display library. To obtain mutant single-chain variable-fragment antibodies (scFvs) with improved affinity and immunotoxins with increased activity, we subjected G49 to in vitro affinity maturation by a complementarity-determining-region (CDR) random-mutagenesis technique. Using light-chain CDR3 mutagenesis, cell-based panning by phage display, subsequent heavy-chain CDR1 mutagenesis, and flow-cytometric selection by yeast-surface display, we generated the mutant scFv clone 902V, with an overall 11-fold increase in affinity for GPNMB. Clone 902V was further randomized throughout the whole scFv by error-prone PCR, and one mutant, F6V, was selected by yeast-surface display. F6V scFv, differing from 902V by one amino-acid change in the light-chain CDR2, exhibited an affinity for GPNMB of 0.30 nM. The F6V mutant scFv clone was fused with a truncated form of Pseudomonas exotoxin A to form the immunotoxin F6V-PE38. F6V-PE38 demonstrated significant protein-synthesis-inhibition activity on GPNMB-expressing glioma and malignant melanoma cells (IC(50) = 0.5 ng/ml [8 pM]), a 60-fold improvement over G49 activity, but no cytotoxicity on GPNMB-negative cells. Furthermore, F6V-PE38 exhibited significant antitumor activity against subcutaneous malignant glioma xenografts in two nude-mouse models and a melanoma neoplastic meningitis model in athymic rats. These GPNMB-specific scFv antibodies and immunotoxins hold promise as reagents in targeted therapy for HGGs and other GPNMB-expressing malignancies.

Indexed as

AnimalsCell Line, TumorChromatography, AffinityFlow CytometryGliomaHumansImmunotoxinsMelanomaMembrane GlycoproteinsMiceMice, NudeRecombinant Fusion ProteinsSurface Plasmon ResonanceGPNMB protein, humanImmunotoxinsMembrane GlycoproteinsRecombinant Fusion Proteins

Identifiers

PMID20824708
PMCPMC3024457
OpenAlexW1980163964

What OpenQuestion holds

Textmetadata
LicenceTDM
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.