Evidence map›Paper›PMID 20925961›Full record

ArticleBMC biotechnology2010

Development of an EGFRvIII specific recombinant antibody.

Puja Gupta, Shuang-Yin Han, Marina Holgado-Madruga, Siddhartha S Mitra, Gordon Li, Ryan T Nitta, Albert J Wong

Open access · goldAbstract read
In one paragraph

Article in BMC biotechnology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.0field-weighted citation impact, top 7% 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, 60 citations in OpenAlex.

  1. Review
  2. Antigen-Dependent Inducible T-Cell Reporter System for PET Imaging of Breast Cancer and Glioblastoma.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2023
    Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. EGFRJournal of oncology · 2019
    Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Antiproliferative and apoptotic effects of a specific anti-insulin-like growth factor I receptor single chain antibody on breast cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Article
  18. Article
  19. NK cell-based immunotherapies in Pediatric Oncology.Journal of pediatric hematology/oncology · 2015
    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

7 authors at 3 institutions in 2 countries.

Puja GuptaBrain Tumor Research Laboratories, Department of Neurosurgery, and Program in Cancer Biology, Stanford University Medical Center, Stanford, CA 94305, USA. ajwong@stanford.edu
Shuang-Yin Han
Marina Holgado-Madruga
Siddhartha S Mitra
Gordon Li
Ryan T Nitta
Albert J Wong
Stanford Medicine · USStanford University · USHenan Provincial People's Hospital · CN

Funding

NOVEL EFFECTORS OF GRB2 IN HUMAN GLIAL TUMORSR01CA069495 · NCI · THOMAS JEFFERSON UNIVERSITY · PI WONG, ALBERT J. · 1996 to 2009
$2.8M
A Phase I Study of EGFRvIII Peptide Vaccination (CDX-110) after Conventional RadiRC2CA148491 · NCI · STANFORD UNIVERSITY · PI FISHER, PAUL GRAHAM, WONG, ALBERT J. · 2009 to 2010
$1.5M
Using Insights from EGFRvIII to Improve EGFR Directed Therapy in Human GliomasR01CA124832 · NCI · STANFORD UNIVERSITY · PI WONG, ALBERT J. · 2007 to 2011
$1.5M
NCI NIH HHS CA124832NCI NIH HHS CA148491NCI NIH HHS CA69495
6 · The paper itself

Abstract

backgroundEGF receptor variant III (EGFRvIII) is the most common variant of the EGF receptor observed in human tumors. It results from the in frame deletion of exons 2-7 and the generation of a novel glycine residue at the junction of exons 1 and 8. This novel juxtaposition of amino acids within the extra-cellular domain of the EGF receptor creates a tumor specific and immunogenic epitope. EGFRvIII expression has been seen in many tumor types including glioblastoma multiforme (GBM), breast adenocarcinoma, non-small cell lung carcinoma, ovarian adenocarcinoma and prostate cancer, but has been rarely observed in normal tissue. Because this variant is tumor specific and highly immunogenic, it can be used for both a diagnostic marker as well as a target for immunotherapy. Unfortunately many of the monoclonal and polyclonal antibodies directed against EGFRvIII have cross reactivity to wild type EGFR or other non-specific proteins. Furthermore, a monoclonal antibody to EGFRvIII is not readily available to the scientific community.

resultsIn this study, we have developed a recombinant antibody that is specific for EGFRvIII, has little cross reactivity for the wild type receptor, and which can be easily produced. We initially designed a recombinant antibody with two anti-EGFRvIII single chain Fv's linked together and a human IgG1 Fc component. To enhance the specificity of this antibody for EGFRvIII, we mutated tyrosine H59 of the CDRH2 domain and tyrosine H105 of the CDRH3 domain to phenylalanine for both the anti-EGFRvIII sequence inserts. This mutated recombinant antibody, called RAb(DMvIII), specifically detects EGFRvIII expression in EGFRvIII expressing cell lines as well as in EGFRvIII expressing GBM primary tissue by western blot, immunohistochemistry (IHC) and immunofluorescence (IF) and FACS analysis. It does not recognize wild type EGFR in any of these assays. The affinity of this antibody for EGFRvIII peptide is 1.7 × 10⁷ M⁻¹ as determined by enzyme-linked immunosorbent assay (ELISA).

conclusionThis recombinant antibody thus holds great potential to be used as a research reagent and diagnostic tool in research laboratories and clinics because of its high quality, easy viability and unique versatility. This antibody is also a strong candidate to be investigated for further in vivo therapeutic studies.

Indexed as

Antibody SpecificityAnimalsAntibody AffinityCell Line, TumorCross ReactionsEpitopesErbB ReceptorsHumansMiceMice, Inbred NODMice, SCIDMutagenesis, Site-DirectedNeoplasms, ExperimentalRecombinant ProteinsSingle-Chain Antibodiesepidermal growth factor receptor VIIIEpitopesErbB ReceptorsRecombinant ProteinsSingle-Chain Antibodies

Identifiers

PMID20925961
PMCPMC2959087
OpenAlexW1999608575

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.