Evidence map›Paper›PMID 26910291›Full record

ArticlemAbs

Differential killing of CD56-expressing cells by drug-conjugated human antibodies targeting membrane-distal and membrane-proximal non-overlapping epitopes.

Yang Feng, Yanping Wang, Zhongyu Zhu, Wei Li, Robyn T Sussman, Michael Randall, Kristopher R Bosse, John M Maris, Dimiter S Dimitrov

Abstract read
In one paragraph

Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
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

18 citing papers in PubMed.

  1. Article
  2. Article
  3. Immunotherapy of Neuroblastoma: Facts and Hopes.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
    Review
  4. Article
  5. Article
  6. Review
  7. Targets and Antibody Formats for Immunotherapy of Neuroblastoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020
    Review
  8. Article
  9. Comprehensive Transcriptome Profiling of CrypticClinical cancer research : an official journal of the American Association for Cancer Research · 2020
    Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. 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

9 authors.

Yang Fenga Protein Interactions Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute , Frederick , MD , USA.
Yanping Wanga Protein Interactions Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute , Frederick , MD , USA.
Zhongyu Zhua Protein Interactions Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute , Frederick , MD , USA.
Wei Lia Protein Interactions Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute , Frederick , MD , USA.
Robyn T Sussmanc Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia , Philadelphia , PA , USA.
Michael Randallc Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia , Philadelphia , PA , USA.
Kristopher R Bossec Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia , Philadelphia , PA , USA.
John M Marisc Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia , Philadelphia , PA , USA.
Dimiter S Dimitrova Protein Interactions Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute , Frederick , MD , USA.

Funding

Human Monoclonal Antibodies Against CancerZIABC010701 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI DIMITROV, DIMITER S · 2009 to 2017
$6.9M
6 · The paper itself

Abstract

CD56 (NCAM, neural cell adhesion molecule) is over-expressed in many tumor types, including neuroblastoma, multiple myeloma, small cell lung cancer, ovarian cancer, acute myeloid leukemia, NK-T lymphoma, neuroendocrine cancer and pancreatic cancer. Using phage display, we identified 2 high-affinity anti-CD56 human monoclonal antibodies (mAbs), m900 and m906, which bound to spatially separated non-overlapping epitopes with similar affinity (equilibrium dissociation constant 2.9 and 4.5 nM, respectively). m900 bound to the membrane proximal fibronectin type III-like domains, whereas m906 bound to the N-terminal IgG-like domains. m906 induced significant down-regulation of CD56 in 4 neuroblastoma cell lines tested, while m900-induced downregulation of CD56 was much lower. Antibody-drug conjugates (ADCs) made by conjugation with a highly potent pyrrolobenzodiazepine dimer (PBD) exhibited killing activity that correlated with CD56 down-regulation, and to some extent with in vivo binding ability of the antibodies. The m906PBD ADC was much more potent than m900PBD, likely due to higher CD56-mediated downregulation and stronger binding to cells. Treatment with m906PBD ADC resulted in very potent cytotoxicity (IC50: 0.05-1.7 pM). These results suggest a novel approach for targeting CD56-expressing neuroblastoma cells. Further studies in animal models and in humans are needed to find whether these antibodies and their drug conjugates are promising candidate therapeutics.

Indexed as

AnimalsAntibodies, MonoclonalAntibody AffinityAntineoplastic AgentsCD56 AntigenCell Line, TumorCell SurvivalEpitopesHumansImmunoconjugatesNeuroblastomaXenograft Model Antitumor AssaysAntibodies, MonoclonalAntineoplastic AgentsCD56 AntigenEpitopesImmunoconjugatesNCAM1 protein, humanAntibody-drug conjugatesCD56 internalizationCD56-targeting therapyneuroblastomaPBDtherapeutic antibodies

Identifiers

PMID26910291
PMCPMC4966860

What OpenQuestion holds

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Registered trials

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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.