Evidence map›Paper›PMID 37091063›Full record

ArticleBioactive materials2023

Engineered human pluripotent stem cell-derived natural killer cells with PD-L1 responsive immunological memory for enhanced immunotherapeutic efficacy.

Yun Chang, Gyuhyung Jin, Weichuan Luo, Qian Luo, Juhyung Jung, Sydney N Hummel, Sandra Torregrosa-Allen, Bennett D Elzey, Philip S Low, Xiaojun Lance Lian and 1 more

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

Article in Bioactive materials, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

25 citing papers in PubMed, 30 citations in OpenAlex.

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  20. Manufacturing CAR-NK against tumors: Who is the ideal supplier?Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024
    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

11 authors at 2 institutions in 1 country.

Yun ChangDavidson School of Chemical Engineering, Purdue University, West Lafayette, IN, 47907, USA.
Gyuhyung JinDavidson School of Chemical Engineering, Purdue University, West Lafayette, IN, 47907, USA.
Weichuan LuoDepartment of Chemistry, Purdue University, West Lafayette, IN, 47907, USA.
Qian LuoDepartment of Chemistry, Purdue University, West Lafayette, IN, 47907, USA.
Juhyung JungDavidson School of Chemical Engineering, Purdue University, West Lafayette, IN, 47907, USA.
Sydney N HummelDavidson School of Chemical Engineering, Purdue University, West Lafayette, IN, 47907, USA.
Sandra Torregrosa-AllenPurdue University Institute for Cancer Research, West Lafayette, IN, 47907, USA.
Bennett D ElzeyPurdue University Institute for Cancer Research, West Lafayette, IN, 47907, USA.
Philip S LowPurdue University Institute for Cancer Research, West Lafayette, IN, 47907, USA.
Xiaojun Lance LianDepartment of Biomedical Engineering, The Huck Institutes of the Life Sciences, Department of Biology, The Pennsylvania State University, University Park, PA, 16802, USA.
Xiaoping BaoDavidson School of Chemical Engineering, Purdue University, West Lafayette, IN, 47907, USA.
Purdue University West Lafayette · USPennsylvania State University · US

Funding

Engineer Biomimetic Microfluidic Models to Investigate and Reprogram Tumor Associated Neutrophils for Cancer TherapyR37CA265926 · NCI · PURDUE UNIVERSITY · PI Xiaoping Bao · 2022 to 2026
$1.7M
NCI NIH HHS R37 CA265926
6 · The paper itself

Abstract

Adoptive chimeric antigen receptor (CAR)-engineered natural killer (NK) cells have shown promise in treating various cancers. However, limited immunological memory and access to sufficient numbers of allogenic donor cells have hindered their broader preclinical and clinical applications. Here, we first assess eight different CAR constructs that use an anti-PD-L1 nanobody and/or universal anti-fluorescein (FITC) single-chain variable fragment (scFv) to enhance antigen-specific proliferation and anti-tumor cytotoxicity of NK-92 cells against heterogenous solid tumors. We next genetically engineer human pluripotent stem cells (hPSCs) with optimized CARs and differentiate them into functional dual CAR-NK cells. The tumor microenvironment responsive anti-PD-L1 CAR effectively promoted hPSC-NK cell proliferation and cytotoxicity through antigen-dependent activation of phosphorylated STAT3 (pSTAT3) and pSTAT5 signaling pathways via an intracellular truncated IL-2 receptor β-chain (ΔIL-2Rβ) and STAT3-binding tyrosine-X-X-glutamine (YXXQ) motif. Anti-tumor activities of PD-L1-induced memory-like hPSC-NK cells were further boosted by administering a FITC-folate bi-specific adapter that bridges between a programmable anti-FITC CAR and folate receptor alpha-expressing breast tumor cells. Collectively, our hPSC CAR-NK engineering platform is modular and could constitute a realistic strategy to manufacture off-the-shelf CAR-NK cells with immunological memory-like phenotype for targeted immunotherapy.

Indexed as

Chimeric antigen receptorHuman pluripotent stem cellsImmunological memoryImmunotherapyNatural killer cells

Identifiers

PMID37091063
PMCPMC10113709
OpenAlexW4362631363

What OpenQuestion holds

Textmetadata
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.