Evidence map›Paper›PMID 21862685›Full record

ArticleMolecular cancer therapeutics2011

Targeting tumor-initiating cancer cells with dCD133KDEL shows impressive tumor reductions in a xenotransplant model of human head and neck cancer.

Nate N Waldron, Dan S Kaufman, Seunguk Oh, Zintis Inde, Melinda K Hexum, John R Ohlfest, Daniel A Vallera

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cancer therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
3.4field-weighted citation impact, top 6% 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

39 citing papers in PubMed, 76 citations in OpenAlex.

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  11. Cancer stem cells and strategies for targeted drug delivery.Drug delivery and translational research · 2021
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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 2 institutions in 1 country.

Nate N WaldronDepartment of Pharmacology, Masonic Cancer Center, University of Minnesota, MMC: 367, Minneapolis, MN 55455, USA.
Dan S Kaufman
Seunguk Oh
Zintis Inde
Melinda K Hexum
John R Ohlfest
Daniel A Vallera
Minneapolis Institute of Arts · USUniversity of Minnesota · US

Funding

IMMUNOTOXINS IN HUMAN BONE MARROW TRANSPLANTATIONR01CA036725 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI VALLERA, DANIEL A · 1985 to 2015
$3.3M
Hematopoietic precursor development from human ES cellsR01HL077923 · NHLBI · UNIVERSITY OF MINNESOTA · PI KAUFMAN, DAN S. · 2006 to 2010
$2.1M
NCI NIH HHS R01 CA036725NCI NIH HHS R01-CA36725NHLBI NIH HHS R01 HL077923
6 · The paper itself

Abstract

A novel anticancer agent was constructed by fusing a gene encoding the scFV that targets both glycosylated and unglycosylated forms of CD133 to a gene fragment encoding deimmunized PE38KDEL. The resulting fusion protein, dCD133KDEL, was studied to determine its ability to bind and kill tumor-initiating cells in vitro and in vivo. The anti-CD133 scFV selectively bound HEK293 cells transfected with the CD133 receptor gene. Time course viability studies showed that dCD133KDEL selectively inhibited NA-SCC and UMSCC-11B, 2 head and neck squamous cell carcinomas that contain a CD133 expressing subpopulation. Importantly, the drug did not inhibit the viability of hematopoietic lineages measured by long-term culture-initiating cell and colony-forming assays from sorted human CD34+ progenitor cells. In addition to in vitro studies, in vivo tumor initiation experiments confirmed that CD133-sorted cells implanted into the flanks of nude mice grew faster and larger than unsorted cells. In contrast, cells that were pretreated with dCD133KDEL before implantation showed the slowest and lowest incidence of tumors. Furthermore, UMSCC-11B-luc tumors treated with multiple intratumoral injections of dCD133KDEL showed marked growth inhibition, leading to complete degradation of the tumors that was not observed with an irrelevant control-targeted toxin. Experiments in immunocompetent mice showed that toxin deimmunization resulted in a 90% reduction in circulating antitoxin levels. These studies show that dCD133KDEL is a novel anticancer agent effective at inhibiting cell proliferation, tumor initiation, and eliminating established tumors by targeting the CD133 subpopulation. This agent shows significant promise for potential development as a clinically useful therapy.

Indexed as

AC133 AntigenADP Ribose TransferasesAnimalsAntigens, CDBacterial ToxinsCarcinoma, Squamous CellCell Growth ProcessesCell Line, TumorCell SurvivalExotoxinsFemaleGlycoproteinsHead and Neck NeoplasmsHumansImmunoglobulin FragmentsImmunotoxinsAC133 AntigenADP Ribose TransferasesAntigens, CDBacterial ToxinsExotoxinsGlycoproteinsImmunoglobulin FragmentsImmunotoxinsPeptidesPROM1 protein, humanProm1 protein, mousePseudomonas aeruginosa Exotoxin ARecombinant Fusion ProteinsVirulence Factors

Identifiers

PMID21862685
PMCPMC3191276
OpenAlexW2170162759

What OpenQuestion holds

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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.