Evidence map›Paper›PMID 24176543›Full record

ArticleCytotherapy2014

Genetically engineered fixed K562 cells: potent "off-the-shelf" antigen-presenting cells for generating virus-specific T cells.

Kazushi Tanimoto, Pawel Muranski, Samantha Miner, Hiroshi Fujiwara, Sachiko Kajigaya, Keyvan Keyvanfar, Nancy Hensel, A John Barrett, J Joseph Melenhorst

Open access · greenAbstract read
In one paragraph

Article in Cytotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.3field-weighted citation impact, top 37% 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

7 citing papers in PubMed, 7 citations in OpenAlex.

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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 at 3 institutions in 2 countries.

Kazushi TanimotoStem Cell Allogeneic Transplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. Electronic address: kazshi.tanimoto@gmail.com.
Pawel MuranskiStem Cell Allogeneic Transplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Samantha MinerStem Cell Allogeneic Transplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Hiroshi FujiwaraDepartment of Bioregulatory Medicine, Ehime University Graduate School of Medicine, Ehime, Japan.
Sachiko KajigayaStem Cell Allogeneic Transplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Keyvan KeyvanfarStem Cell Allogeneic Transplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
Nancy HenselStem Cell Allogeneic Transplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
A John BarrettStem Cell Allogeneic Transplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
J Joseph MelenhorstStem Cell Allogeneic Transplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA; Abramson Cancer Center, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
National Heart Lung and Blood Institute · USNational Institutes of Health · USEhime University · JP

Funding

GRAFT-VERSUS-LEUKEMIAZ01HL002342 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI BARRETT, AUSTIN JOHN · 1994 to 2008
$7.7M
Intramural NIH HHS Z01 HL002342
6 · The paper itself

Abstract

BACKGROUND

aimsThe human leukemia cell line K562 represents an attractive platform for creating artificial antigen-presenting cells (aAPC). It is readily expandable, does not express human leukocyte antigen (HLA) class I and II and can be stably transduced with various genes.

methodsIn order to generate cytomegalovirus (CMV) antigen-specific T cells for adoptive immunotherapy, we transduced K562 with HLA-A∗0201 in combination with co-stimulatory molecules.

resultsIn preliminary experiments, irradiated K562 expressing HLA-A∗0201 and 4-1BBL pulsed with CMV pp65 and IE-1 peptide libraries failed to elicit antigen-specific CD8⁺ T cells in HLA-A∗0201⁺ peripheral blood mononuclear cells (PBMC) or isolated T cells. Both wild-type K562 and aAPC strongly inhibited T cell proliferation to the bacterial superantigen staphylococcal enterotoxin B (SEB) and OKT3 and in mixed lymphocyte reaction (MLR). Transwell experiments suggested that suppression was mediated by a soluble factor; however, MLR inhibition was not reversed using transforming growth factor-β blocking antibody or prostaglandin E2 inhibitors. Full abrogation of the suppressive activity of K562 on MLR, SEB and OKT3 stimulation was only achieved by brief fixation with 0.1% formaldehyde. Fixed, pp65 and IE-1 peptide-loaded aAPC induced robust expansion of CMV-specific T cells.

conclusionsFixed gene-modified K562 can serve as effective aAPC to expand CMV-specific cytotoxic T lymphocytes for therapeutic use in patients after stem cell transplantation. Our findings have implications for broader understanding of the immune evasion mechanisms used by leukemia and other tumors.

Indexed as

Genetic EngineeringAntigen-Presenting CellsCD8-Positive T-LymphocytesCytomegalovirus InfectionsHLA AntigensHumansK562 CellsLeukocytes, MononuclearLymphocyte ActivationT-Lymphocytes, CytotoxicHLA Antigensartificial APCcytomegaloviruscytotoxic T cellfixation

Identifiers

PMID24176543
PMCPMC6755681
OpenAlexW2095360152

What OpenQuestion holds

Textmetadata
LicenceTDM
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.