Evidence map›Paper›PMID 26566946›Full record

ArticleTargeted oncology2016

Heterodimeric Bispecific Single Chain Variable Fragments (scFv) Killer Engagers (BiKEs) Enhance NK-cell Activity Against CD133+ Colorectal Cancer Cells.

J U Schmohl, M K Gleason, P R Dougherty, J S Miller, D A Vallera

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

Article in Targeted oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 6% 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

69 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.

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  19. Cell Therapy as Target Therapy against Colon Cancer Stem Cells.International journal of molecular sciences · 2023
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9 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

5 authors at 2 institutions in 2 countries.

J U SchmohlUniversity of Minnesota Masonic Cancer Center, Section of Molecular Cancer Therapeutics, Therapeutic Radiology-Radiation Oncology, University of Minnesota, Minneapolis, MN, USA.
M K GleasonUniversity of Minnesota Masonic Cancer Center, Adult Division of Hematology, Oncology and Transplantation Oncology, University of Minnesota, Minneapolis, MN, USA.
P R DoughertyUniversity of Minnesota Masonic Cancer Center, Section of Molecular Cancer Therapeutics, Therapeutic Radiology-Radiation Oncology, University of Minnesota, Minneapolis, MN, USA.
J S MillerUniversity of Minnesota Masonic Cancer Center, Adult Division of Hematology, Oncology and Transplantation Oncology, University of Minnesota, Minneapolis, MN, USA.
D A ValleraUniversity of Minnesota Masonic Cancer Center, Section of Molecular Cancer Therapeutics, Therapeutic Radiology-Radiation Oncology, University of Minnesota, Minneapolis, MN, USA. valle001@umn.edu.
University of Minnesota Medical Center · USMinnesota Oncology · US

Funding

Viral priming and targeting NK cells against solid tumor malignanciesR35CA197292 · NCI · UNIVERSITY OF MINNESOTA · PI MILLER, JEFFREY S. · 2015 to 2021
$6.2M
Translational Pediatric Cancer Epidemiology Research Training GrantT32CA099936 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Logan G. Spector · 2004 to 2026
$5.1M
IMMUNOTOXINS IN HUMAN BONE MARROW TRANSPLANTATIONR01CA036725 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI VALLERA, DANIEL A · 1985 to 2015
$3.3M
NCI NIH HHS R01 CA036725NCI NIH HHS R35 CA197292NCI NIH HHS T32 CA099936
6 · The paper itself

Abstract

backgroundNatural killer (NK) cells are potent cytotoxic lymphocytes that play a critical role in tumor immunosurveillance and control. Cancer stem cells (CSC) initiate and sustain tumor cell growth, mediate drug refractory cancer relapse, and express the well-known surface marker CD133.

methodsDNA fragments from two fully humanized single chain fragment variable (scFv) antibodies recognizing CD16 on NK-cells and CD133 on CSC were genetically spliced forming a novel drug, 16 × 133 BiKE that simultaneously recognizes these antigens to facilitate an immunologic synapse. The anti-CD133 was created using a fusion protein prepared by fusing DNA fragments encoding the two extracellular domains of CD133. Immunization of mice with the resulting fusion protein generated a unique antibody that recognized the molecular framework and was species cross-reactive.

resultsIn vitro chromium-51 ((51)Cr) release cytotoxicity assays at both high and low effector:target ratios demonstrated the ability of the heterodimeric biological drug to greatly enhance NK-cell killing of human Caco-2 colorectal carcinoma cells known to overexpress CD133. The tumor associated antigen specificity of the drug for CD133 even enhanced NK-cell cytotoxicity against the NK-resistant human Burkitt's lymphoma Daudi cell line, which has less than 5 % CD133 surface expression. Flow cytometry analysis revealed increases in NK-cell degranulation and Interferon-γ production upon co-culture with Caco-2 targets in the presence of the drug.

conclusionThese studies demonstrate that the innate immune system can be effectively recruited to kill CSC using bispecific antibodies targeting CD133 and that this anti-CD133 scFv may be useful in this bispecific platform or perhaps in the design of more complex trispecific molecules for carcinoma therapy.

Indexed as

AC133 AntigenAnimalsAntigens, NeoplasmColorectal NeoplasmsHumansKiller Cells, NaturalMiceSingle-Chain AntibodiesAC133 AntigenAntigens, NeoplasmProm1 protein, mouseSingle-Chain Antibodies

Identifiers

PMID26566946
PMCPMC4873478
OpenAlexW2174882175

What OpenQuestion holds

Textmetadata
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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.