Evidence map›Paper›PMID 23085102›Full record

ArticleToxicology in vitro : an international journal published in association with BIBRA2013

Insights into the mechanism of cell death induced by saporin delivered into cancer cells by an antibody fusion protein targeting the transferrin receptor 1.

Tracy R Daniels-Wells, Gustavo Helguera, José A Rodríguez, Lai Sum Leoh, Michael A Erb, Graciel Diamante, David Casero, Matteo Pellegrini, Otoniel Martínez-Maza, Manuel L Penichet

Open access · bronzeAbstract read
In one paragraph

Article in Toxicology in vitro : an international journal published in association with BIBRA, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

23 citing papers in PubMed, 29 citations in OpenAlex.

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  3. A proimmunotoxin nanodrug targeting AIDS-associated non-Hodgkin lymphoma.Journal of controlled release : official journal of the Controlled Release Society · 2026
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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

10 authors at 2 institutions in 1 country.

Tracy R Daniels-WellsDivision of Surgical Oncology, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. tdaniels@mednet.ucla.edu
Gustavo Helguera
José A Rodríguez
Lai Sum Leoh
Michael A Erb
Graciel Diamante
David Casero
Matteo Pellegrini
Otoniel Martínez-Maza
Manuel L Penichet
University of California, Los Angeles · USUniversity of California System · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHEN, IRVIN S.Y. · 1991 to 2018
$39.9M
IMMUNE DYSFUNCTION AND AIDS-ASSOCIATED B-CELL LYMPHOMAR01CA057152 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MARTINEZ-MAZA, OTONIEL · 1992 to 2009
$2.7M
Anti-TfR IgG3-Av: A New Drug Against Multiple MyelomaR01CA107023 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PENICHET, MANUEL L · 2005 to 2009
$1.7M
Antibody-mediated Gene Therapy for the Treatment of CancerK01CA138559 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DANIELS-WELLS, TRACY RUTH · 2009 to 2013
$704k
Howard Hughes Medical InstituteNCI NIH HHS CA16042NCI NIH HHS K01 CA138559NCI NIH HHS K01CA138559NCI NIH HHS P30 CA016042NCI NIH HHS R01 CA057152NCI NIH HHS R01 CA107023NCI NIH HHS R01CA107023NCI NIH HHS R01CA57152NIAID NIH HHS AI28697NIAID NIH HHS P30 AI028697PHS HHS CJX1-44835-WS-29646
6 · The paper itself

Abstract

We previously developed an antibody-avidin fusion protein (ch128.1Av) that targets the human transferrin receptor 1 (TfR1) and exhibits direct cytotoxicity against malignant B cells in an iron-dependent manner. ch128.1Av is also a delivery system and its conjugation with biotinylated saporin (b-SO6), a plant ribosome-inactivating toxin, results in a dramatic iron-independent cytotoxicity, both in malignant cells that are sensitive or resistant to ch128.1Av alone, in which the toxin effectively inhibits protein synthesis and triggers caspase activation. We have now found that the ch128.1Av/b-SO6 complex induces a transcriptional response consistent with oxidative stress and DNA damage, a response that is not observed with ch128.1Av alone. Furthermore, we show that the antioxidant N-acetylcysteine partially blocks saporin-induced apoptosis suggesting that oxidative stress contributes to DNA damage and ultimately saporin-induced cell death. Interestingly, the toxin was detected in nuclear extracts by immunoblotting, suggesting the possibility that saporin might induce direct DNA damage. However, confocal microscopy did not show a clear and consistent pattern of intranuclear localization. Finally, using the long-term culture-initiating cell assay we found that ch128.1Av/b-SO6 is not toxic to normal human hematopoietic stem cells suggesting that this critical cell population would be preserved in therapeutic interventions using this immunotoxin.

Indexed as

AnimalsAntigens, CDAntineoplastic Agents, PhytogenicApoptosisAvidinCell DeathCell LineCell Line, TumorCell ProliferationGene Expression ProfilingHumansImmunoglobulin GMiceNeoplasmsReceptors, TransferrinRecombinant Fusion ProteinsAntigens, CDAntineoplastic Agents, PhytogenicAvidinCD71 antigenImmunoglobulin GReceptors, TransferrinRecombinant Fusion ProteinsRibosome Inactivating Proteins, Type 1Saporins

Identifiers

PMID23085102
PMCPMC3513587
OpenAlexW2125873159

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.