Evidence map›Paper›PMID 26487683›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Agonist antibody that induces human malignant cells to kill one another.

Kyungmoo Yea, Hongkai Zhang, Jia Xie, Teresa M Jones, Chih-Wei Lin, Walter Francesconi, Fulvia Berton, Mohammad Fallahi, Karsten Sauer, Richard A Lerner

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

12 citing papers in PubMed, 19 citations in OpenAlex.

  1. Technologies for Monoclonal Antibody Discovery and Development.International journal of molecular sciences · 2025
    Review
  2. Target neutrophil heterogeneity and plasticity in cancer.Journal of hematology & oncology · 2025
    Review
  3. Review
  4. Review
  5. Review
  6. Selection of a Full Agonist Combinatorial Antibody that Rescues Leptin Deficiency In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Activating pleiotropic receptors to kill cancer cells.Cell cycle (Georgetown, Tex.) · 2016
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 2 countries.

Kyungmoo YeaShanghai Institute for Advanced Immunological Studies, ShanghaiTech University, Shanghai 200031, China;
Hongkai ZhangDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037;
Jia XieDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037;
Teresa M JonesDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037;
Chih-Wei LinDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037;
Walter FrancesconiDepartment of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA 92037;
Fulvia BertonDepartment of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037;
Mohammad FallahiBioInformatics Core, The Scripps Research Institute, Scripps Florida, Jupiter, FL 33458;
Karsten SauerDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037.
Richard A LernerDepartment of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037; rlerner@scripps.edu.
Scripps Research Institute · USShanghaiTech University · CN

Funding

Howard Hughes Medical Institute
6 · The paper itself

Abstract

An attractive, but as yet generally unrealized, approach to cancer therapy concerns discovering agents that change the state of differentiation of the cancer cells. Recently, we discovered a phenomenon that we call "receptor pleiotropism" in which agonist antibodies against known receptors induce cell fates that are very different from those induced by the natural agonist to the same receptor. Here, we show that one can take advantage of this phenomenon to convert acute myeloblastic leukemic cells into natural killer cells. Upon induction with the antibody, these leukemic cells enter into a differentiation cascade in which as many as 80% of the starting leukemic cells can be differentiated. The antibody-induced killer cells make large amounts of perforin, IFN-γ, and granzyme B and attack and kill other members of the leukemic cell population. Importantly, induction of killer cells is confined to transformed cells, in that normal bone marrow cells are not induced to form killer cells. Thus, it seems possible to use agonist antibodies to change the differentiation state of cancer cells into those that attack and kill other members of the malignant clone from which they originate.

Indexed as

AntibodiesBlotting, WesternCell- and Tissue-Based TherapyCell DifferentiationComputational BiologyFlow CytometryGranzymesHumansImmunohistochemistryInterferon-gammaKiller Cells, NaturalLeukemia, Myeloid, AcuteMicroscopy, Electron, ScanningPerforinAntibodiesGranzymesInterferon-gammaPerforinagonist antibodycombinatorial antibody librariesdifferentiationnatural killer cell

Identifiers

PMID26487683
PMCPMC4653151
OpenAlexW2105876369

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.