Evidence map›Paper›PMID 21791637›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011

HER2-affitoxin: a potent therapeutic agent for the treatment of HER2-overexpressing tumors.

Rafal Zielinski, Ilya Lyakhov, Moinuddin Hassan, Monika Kuban, Kimberly Shafer-Weaver, Amir Gandjbakhche, Jacek Capala

Open access · bronzeAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.4field-weighted citation impact, top 8% 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

22 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Fighting Cancer with Bacteria and Their Toxins.International journal of molecular sciences · 2021
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Affibody molecules as engineered protein drugs.Experimental & molecular medicine · 2017
    Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  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

7 authors at 4 institutions in 2 countries.

Rafal ZielinskiRadiation Oncology Branch, Center for Cancer Research, National Cancer Institute (NCI), Section on Analytical and Functional Biophotonics, Program on Pediatric Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.
Ilya Lyakhov
Moinuddin Hassan
Monika Kuban
Kimberly Shafer-Weaver
Amir Gandjbakhche
Jacek Capala
Center for Cancer Research · USEunice Kennedy Shriver National Institute of Child Health and Human Development · USNational Cancer Institute · USJohn Paul II Catholic University of Lublin · PL

Funding

Quantitative Biophotonics for Tissue Characterization and FunctionZIAHD000261 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI GANDJBAKHCHE, AMIR H · 2009 to 2025
$13.6M
Molecular Imaging and Targeted Therapy of HER2-Positive Breast CancersZIABC010727 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI CAPALA, JACEK · 2009 to 2011
$2.0M
Intramural NIH HHS ZIA BC010727NCI NIH HHS N01 CO012400NCI NIH HHS N01-CO-12400NCI NIH HHS N01-CO-12401NCI NIH HHS N02 CO012401
6 · The paper itself

Abstract

purposeCancers overexpressing the HER2/neu gene are usually more aggressive and are associated with poor prognosis. Although trastuzumab has significantly improved the outcome, many tumors do not respond or acquire resistance to current therapies. To provide an alternative HER2-targeted therapy, we have developed and characterized a novel recombinant protein combining an HER2-specific Affibody and modified Pseudomonas aeruginosa exotoxin A (PE 38), which, after binding to HER2, is internalized and delivered to the cytosol of the tumor cell, where it blocks protein synthesis by ADP ribosylation of eEF-2. EXPERIMENTAL

designThe effect of the Affitoxin on cell viability was assessed using CellTiter-Glo (Promega). To assess HER2-specific efficacy, athymic nude mice bearing BT-474 breast cancer, SK-OV-3 ovarian cancer, and NCI-N87 gastric carcinoma xenografts were treated with the Affitoxin (HER2- or Tag-specific), which was injected every third day. Affitoxin immunogenicity in female BALB/c mice was investigated using standard antibody production and splenocyte proliferation assays.

resultsIn vitro experiments proved that HER2-Affitoxin is a potent agent that eliminates HER2-overexpressing cells at low picomolar concentrations. Therapeutic efficacy studies showed complete eradication of relatively large BT-474 tumors and significant effects on SK-OV-3 and NCI-N87 tumors. HER2-Affitoxin cleared quickly from circulation (T(1/2) < 10 minutes) and was well tolerated by mice at doses of 0.5 mg/kg and below. Immunogenicity studies indicated that HER2-Affitoxin induced antibody development after the third injected dose.

conclusionsOur findings showed that HER2-Affitoxin is an effective anticancer agent and a potential candidate for clinical studies.

Indexed as

ADP Ribose TransferasesAnimalsBacterial ToxinsCell Line, TumorErb-b2 Receptor Tyrosine KinasesExotoxinsImmunotoxinsMiceMice, NudePseudomonas aeruginosa Exotoxin ARecombinant Fusion ProteinsVirulence FactorsXenograft Model Antitumor AssaysADP Ribose TransferasesBacterial ToxinsErb-b2 Receptor Tyrosine KinasesExotoxinsHER2 affitoxinImmunotoxinsPseudomonas aeruginosa Exotoxin ARecombinant Fusion ProteinsVirulence Factors

Identifiers

PMID21791637
PMCPMC3149757
OpenAlexW2171682368

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.