Evidence map›Paper›PMID 25987253›Full record

ArticleLeukemia2015

Affinity maturation of T-cell receptor-like antibodies for Wilms tumor 1 peptide greatly enhances therapeutic potential.

Q Zhao, M Ahmed, D V Tassev, A Hasan, T-Y Kuo, H-F Guo, R J O'Reilly, N-K V Cheung

Open access · greenAbstract read
In one paragraph

Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
3.2field-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

60 citing papers in PubMed, 81 citations in OpenAlex.

  1. Article
  2. Article
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  4. Review
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  6. Review
  7. Preclinical evaluation of a novel CAR-T therapy utilizing a scFv antibody highly specific to MAGE-A4Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Article
  8. Evolution and synthetic biology.Current opinion in microbiology · 2023
    Review
  9. Recent Progress in Antibody Epitope Prediction.Antibodies (Basel, Switzerland) · 2023
    Review
  10. Article
  11. UnderstandingCancers · 2023
    Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. Review
  19. TARP as antigen in cancer immunotherapy.Cancer immunology, immunotherapy : CII · 2021
    Review
  20. Potent, Selective CARs as Potential T-Cell Therapeutics for HPV-positive Cancers.Journal of immunotherapy (Hagerstown, Md. : 1997) · 2021
    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

8 authors at 1 institution in 1 country.

Q ZhaoDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
M AhmedDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-7305-0012
D V TassevDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
A HasanDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
T-Y KuoDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
H-F GuoDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
R J O'ReillyDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
N-K V CheungDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Memorial Sloan Kettering Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
T LYMPHOCYTE SUBSET FUNCTION POST-TRANSPLANTATIONP01CA023766 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI PAMER, ERIC G. · 1985 to 2023
$59.0M
NCI NIH HHS 2 P30 CA008748-48NCI NIH HHS P01 CA023766NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

WT1126 (RMFPNAPYL) is a human leukocyte antigen-A2 (HLA-A2)-restricted peptide derived from Wilms tumor protein 1 (WT1), which is widely expressed in a broad spectrum of leukemias, lymphomas and solid tumors. A novel T-cell-receptor (TCR)-like single-chain variable fragment (scFv) antibody specific for the T-cell epitope consisting of the WT1/HLA-A2 complex was isolated from a human scFv phage library. This scFv was affinity-matured by mutagenesis combined with yeast display and structurally analyzed using a homology model. This monovalent scFv showed a 100-fold affinity improvement (dissociation constant (KD)=3 nm) and exquisite specificity towards its targeted epitope or HLA-A2(+)/WT1(+) tumor cells. Bivalent scFv-huIgG1-Fc fusion protein demonstrated an even higher avidity (KD=2 pm) binding to the T-cell epitope and to tumor targets and was capable of mediating antibody-dependent cell-mediated cytotoxicity or tumor lysis by chimeric antigen receptor-expressing human T- or NK-92-MI-transfected cells. This antibody demonstrated specific and potent cytotoxicity in vivo towards WT1-positive leukemia xenograft that was HLA-A2 restricted. In summary, T-cell epitopes can provide novel targets for antibody-based therapeutics. By combining phage and yeast displays and scFv-Fc fusion platforms, a strategy for developing high-affinity TCR-like antibodies could be rapidly explored for potential clinical development.

Indexed as

Antibody AffinityAnimalsCell Line, TumorEpitope MappingEpitopes, T-LymphocyteHLA-A2 AntigenHumansKiller Cells, NaturalLeukemiaMaleMicePeptide FragmentsPeptide LibraryReceptors, Antigen, T-CellSingle-Chain AntibodiesWT1 ProteinsEpitopes, T-LymphocyteHLA-A2 AntigenPeptide FragmentsPeptide LibraryReceptors, Antigen, T-CellSingle-Chain AntibodiesWT1 Proteins

Identifiers

PMID25987253
PMCPMC4788467
OpenAlexW1591828451

What OpenQuestion holds

Textmetadata
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.