Evidence map›Paper›PMID 34282497›Full record

ArticleCancer immunology, immunotherapy : CII2022

Expansion of cytotoxic natural killer cells in multiple myeloma patients using K562 cells expressing OX40 ligand and membrane-bound IL-18 and IL-21.

Jaya Lakshmi Thangaraj, Minh-Trang Thi Phan, SoonHo Kweon, Jinho Kim, Jong-Min Lee, Ilwoong Hwang, Jeehun Park, Junsang Doh, Seung-Hwan Lee, Manh-Cuong Vo and 7 more

Open access · bronzeAbstract read
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

26 citing papers in PubMed, 34 citations in OpenAlex.

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  8. Modulation of NK Cell Properties by ESKAPE Group Bacteria.International journal of molecular sciences · 2025
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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

17 authors at 7 institutions in 3 countries.

Jaya Lakshmi Thangaraj *Research Center for Cancer Immunotherapy, Gwangju, South Korea.
Minh-Trang Thi Phan *Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, South Korea.
SoonHo Kweon *Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, South Korea.
Jinho KimStem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, South Korea.
Jong-Min LeeBio Research Center, Lugensci Co. Ltd., Bucheon, South Korea.
Ilwoong HwangDepartment of Emergency Medicine, Konkuk University Chungju Hospital, Chungju, South Korea.
Jeehun ParkResearch Institute of Advanced Materials, Seoul National University, Seoul, South Korea.
Junsang DohDepartment of Materials Science and Engineering, Seoul National University, Seoul, South Korea.
Seung-Hwan LeeDepartment of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Manh-Cuong VoResearch Center for Cancer Immunotherapy, Gwangju, South Korea.
Tan-Huy ChuResearch Center for Cancer Immunotherapy, Gwangju, South Korea.
Ga-Young SongResearch Center for Cancer Immunotherapy, Gwangju, South Korea.
Seo-Yeon AhnResearch Center for Cancer Immunotherapy, Gwangju, South Korea.
Sung-Hoon JungResearch Center for Cancer Immunotherapy, Gwangju, South Korea.
Hyeoung-Joon KimDepartment of Hematology-Oncology, Chonnam National University Hwasun Hospital, 322 Seoyangro, Hwasun, Jeollanamdo, 519-763, Republic of Korea.
Duck ChoStem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, South Korea. duck.cho@skku.edu.
Je-Jung LeeResearch Center for Cancer Immunotherapy, Gwangju, South Korea. drjejung@chonnam.ac.kr.ORCID http://orcid.org/0000-0002-4635-5697
Chonnam National University Hwasun Hospital · KRChonnam National University · KRSamsung Medical Center · KRSeoul National University · KRKonkuk University · KRPohang University of Science and Technology · KRUniversity of Ottawa · CA

Funding

Ministry of Education, Science and Technology 2020R1A2C2010098National Research Foundation Korea 2018R1A2B6006200
6 · The paper itself

Abstract

backgroundNatural killer (NK) cell-based immunotherapy is a promising treatment approach for multiple myeloma (MM), but obtaining a sufficient number of activated NK cells remains challenging. Here, we report an improved method to generate ex vivo expanded NK (eNK) cells from MM patients based on genetic engineering of K562 cells to express OX40 ligand and membrane-bound (mb) IL-18 and IL-21.

methodsK562-OX40L-mbIL-18/-21 cells were generated by transducing K562-OX40L cells with a lentiviral vector encoding mbIL-18 and mbIL-21, and these were used as feeder cells to expand NK cells from peripheral blood mononuclear cells of healthy donors (HDs) and MM patients in the presence of IL-2/IL-15. Purity, expansion rate, receptor expression, and functions of eNK cells were determined over four weeks of culture.

resultsNK cell expansion was enhanced by short exposure of soluble IL-18 and IL-21 with K562-OX40L cells. Co-culture of NK cells with K562-OX40L-mbIL-18/-21 cells resulted in remarkable expansion of NK cells from HDs (9,860-fold) and MM patients (4,929-fold) over the 28-day culture period. Moreover, eNK cells showed increased expression of major activation markers and enhanced cytotoxicity towards target K562, U266, and RPMI8226 cells.

conclusionsOur data suggest that genetically engineered K562 cells expressing OX40L, mbIL-18, and mbIL-21 improve the expansion of NK cells, increase activation signals, and enhance their cytolytic activity towards MM cells.

Indexed as

Cytotoxicity, ImmunologicCells, CulturedCoculture TechniquesGene ExpressionHumansImmunophenotypingInterleukin-18Interleukin-21InterleukinsK562 CellsKiller Cells, NaturalLymphocyte ActivationMultiple MyelomaOX40 LigandTransduction, GeneticTransgenesIL18 protein, humanInterleukin-18Interleukin-21InterleukinsOX40 LigandIL-18IL-21Multiple MyelomaNK cellsOX40L

Identifiers

PMID34282497
PMCPMC10991462
OpenAlexW3186426676

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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.