Evidence map›Paper›PMID 28231426›Full record

ArticleCancer research and treatment2017

Engineering of Anti-CD133 Trispecific Molecule Capable of Inducing NK Expansion and Driving Antibody-Dependent Cell-Mediated Cytotoxicity.

Jörg U Schmohl, Martin Felices, Felix Oh, Alexander J Lenvik, Aaron M Lebeau, Jayanth Panyam, Jeffrey S Miller, Daniel A Vallera

Open access · diamondAbstract read
In one paragraph

Article in Cancer research and treatment, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 1 pooled it
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

61 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.

  1. Pooled it
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  7. Article
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  9. CD56Journal for immunotherapy of cancer · 2025
    Article
  10. Breaking Immunosuppression to Enhance Cancer Stem Cell-Targeted Immunotherapy.International journal of biological sciences · 2025
    Review
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  15. New immune cell engagers for cancer immunotherapy.Nature reviews. Immunology · 2024
    Review
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1 more citing papers are in PubMed but not listed here.

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 4 institutions in 2 countries.

Jörg U SchmohlDepartment of Therapeutic Radiology-Radiation Oncology, University of Minnesota, Masonic Cancer Center, Minneapolis, MN, USA.
Martin FelicesDepartment of Medicine, Division of Hematology, Oncology, and Transplantation, Minneapolis, MN, USA.
Felix OhDepartment of Therapeutic Radiology-Radiation Oncology, University of Minnesota, Masonic Cancer Center, Minneapolis, MN, USA.
Alexander J LenvikDepartment of Medicine, Division of Hematology, Oncology, and Transplantation, Minneapolis, MN, USA.
Aaron M LebeauDepartment of Pharmacology, University of Minnesota, Minneapolis, MN, USA.
Jayanth PanyamDepartment of Pharmacology, University of Minnesota, Minneapolis, MN, USA.
Jeffrey S MillerDepartment of Medicine, Division of Hematology, Oncology, and Transplantation, Minneapolis, MN, USA.
Daniel A ValleraDepartment of Therapeutic Radiology-Radiation Oncology, University of Minnesota, Masonic Cancer Center, Minneapolis, MN, USA.
Minnesota Oncology · USUniversity of Minnesota · USUniversity of Minnesota Medical Center · USUniversity of Tübingen · DE

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Douglas Yee · 1998 to 2026
$100.4M
Trial Design and Biostatistical Support CoreP01CA065493 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Mark J Osborn · 1995 to 2026
$48.2M
Therapeutic Potential of Adaptive NK Cells in Cancer and TransplantationP01CA111412 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI MILLER, JEFFREY S. · 2005 to 2025
$38.2M
Viral priming and targeting NK cells against solid tumor malignanciesR35CA197292 · NCI · UNIVERSITY OF MINNESOTA · PI MILLER, JEFFREY S. · 2015 to 2021
$6.2M
GVL TO REDUCE AML RELAPSE AFTER MURINE ALLOGENEIC BMTR01CA072669 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI BLAZAR, BRUCE R · 1997 to 2017
$4.9M
IMMUNOTOXINS IN HUMAN BONE MARROW TRANSPLANTATIONR01CA036725 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI VALLERA, DANIEL A · 1985 to 2015
$3.3M
NCI NIH HHS P01 CA065493NCI NIH HHS P01 CA111412NCI NIH HHS P30 CA077598NCI NIH HHS R01 CA036725NCI NIH HHS R01 CA072669NCI NIH HHS R35 CA197292
6 · The paper itself

Abstract

purposeThe selective elimination of cancer stem cells (CSCs) in tumor patients is a crucial goal because CSCs cause drug refractory relapse. To improve the current conventional bispecific immune-engager platform, a 16133 bispecific natural killer (NK) cell engager (BiKE), consisting of scFvs binding FcγRIII (CD16) on NK cells and CD133 on carcinoma cells, was first synthesized and a modified interleukin (IL)-15 crosslinker capable of stimulating NK effector cells was introduced. MATERIALS AND

methodsDNA shuffling and ligation techniques were used to assemble and synthesize the 1615133 trispecific NK cell engager (TriKE). The construct was tested for its specificity using flow cytometry, cytotoxic determinations using chromium release assays, and lytic degranulation. IL-15-mediated expansion was measured using flow-based proliferation assays. The level of interferon (IFN)-γ release was measured because of its importance in the anti-cancer response.

results1615133 TriKE induced NK cell-mediated cytotoxicity and NK expansion far greater than that achieved with BiKE devoid of IL-15. The drug binding and induction of cytotoxic degranulation was CD133+ specific and the anti-cancer activity was improved by integrating the IL-15 cross linker. The NK cell-related cytokine release measured by IFN-γ detection was higher than that of BiKE. NK cytokine release studies showed that although the IFN-γ levels were elevated, they did not approach the levels achieved with IL-12/IL-18, indicating that release was not at the supraphysiologic level.

conclusion1615133 TriKE enhances the NK cell anti-cancer activity and provides a self-sustaining mechanism via IL-15 signaling. By improving the NK cell performance, the new TriKE represents a highly active drug against drug refractory relapse mediated by CSCs.

Indexed as

AC133 AntigenAntibody-Dependent Cell CytotoxicityCell Culture TechniquesCell DegranulationCell Line, TumorCells, CulturedCytotoxicity, ImmunologicGenetic EngineeringHumansImmunotherapyInterferon-gammaInterleukin-15Killer Cells, NaturalLymphocyte ActivationNeoplastic Stem CellsSingle-Chain AntibodiesAC133 AntigenInterferon-gammaInterleukin-15Single-Chain AntibodiesAntibody-dependent cell cytotoxicityCD133Interleukin-15Natural killer cell engagerNeoplastic stem cells

Identifiers

PMID28231426
PMCPMC5654165
OpenAlexW2589601152

What OpenQuestion holds

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LicenceCC BY-NC
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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.