Evidence map›Paper›PMID 35706368›Full record

ArticleCancer communications (London, England)2022

The establishment of polypeptide PSMA-targeted chimeric antigen receptor-engineered natural killer cells for castration-resistant prostate cancer and the induction of ferroptosis-related cell death.

Liyuan Wu, Fei Liu, Le Yin, Fangming Wang, Hui Shi, Qinxin Zhao, Feiya Yang, Dong Chen, Xiying Dong, Yuchun Gu and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cancer communications (London, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.8field-weighted citation impact, top 5% 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

32 citing papers in PubMed, 38 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

11 authors at 5 institutions in 3 countries.

Liyuan WuState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, P. R. China.
Fei LiuState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, P. R. China.
Le YinMolecular Pharmacology Laboratory, Institute of Molecular Medicine, Peking University, Beijing, 100871, P. R. China.
Fangming WangState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, P. R. China.
Hui ShiMolecular Pharmacology Laboratory, Institute of Molecular Medicine, Peking University, Beijing, 100871, P. R. China.
Qinxin ZhaoState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, P. R. China.
Feiya YangState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, P. R. China.
Dong ChenState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, P. R. China.
Xiying DongPeking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, P. R. China.
Yuchun GuMolecular Pharmacology Laboratory, Institute of Molecular Medicine, Peking University, Beijing, 100871, P. R. China.
Nianzeng XingState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, P. R. China.
Chinese Academy of Medical Sciences & Peking Union Medical College · CNPeking University · CNAcademy of Medical Sciences · GBAston University · GBShanxi Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe mortality of castration-resistant prostate cancer (CRPC) is high due to lack of an effective treatment. Chimeric antigen receptor (CAR)-based therapy is a promising immunotherapeutic strategy. Here, we aimed to design a novel CAR-natural killer (NK) cells with a clinically significant tumoricidal effect on CRPC.

methodsWe constructed novel CAR-NK92MI cells with a CD244-based recombinant lentiviral vector. Different intracellular segments (CD244, NKG2D, or CD3ζ) were screened to identify the best candidate according to cell lysis assay and CD107a expression levels. To enhance the affinity of the CAR to the tumor antigen, we compared an antibody specific for prostate-specific membrane antigen (anti-PSMA) with PSMA-targeted polypeptide (p-PSMA), which was screened by phage display combinatorial library. Then, CAR-NK92MI cells with both a high affinity for PSMA and a strong tumoricidal capacity were generated. In addition, we verified their tumor-killing effect in vitro and in vivo. The release of cytokine by NK92MI cells was compared with that by CAR-NK92MI cells through flow cytometry and enzyme-linked immunosorbent assay. Moreover, ferroptosis-related cell death was explored as a possible underlying mechanism.

resultsThree different CAR intracellular regions CAR1 (CD244), CAR2 (CD244, NKG2D) and CAR3 (CD244, NKG2D, and CD3ζ) were constructed. CAR2 was chosen to confer a stronger tumoricidal ability on CAR-NK92MI cells. Compared with anti-PSMA, p-PSMA exhibited enhanced affinity for the tumor antigen. Thus, p-PSMA-CAR-NK92MI cells, which expressed CAR with a polypeptide-based antigen-binding region, an intracellular CD244 and a NKG2D costimulatory domain, were generated. They could selectively and successfully kill PSMA

conclusionsp-PSMA-CAR-NK92MI cells can effectively kill CRPC

Indexed as

FerroptosisProstatic Neoplasms, Castration-ResistantReceptors, Chimeric AntigenAntigens, NeoplasmCell Line, TumorHumansKiller Cells, NaturalMaleNK Cell Lectin-Like Receptor Subfamily KPeptidesAntigens, NeoplasmNK Cell Lectin-Like Receptor Subfamily KPeptidesReceptors, Chimeric AntigenCAR-NK92MIchimeric antigen receptorsimmunotherapyprostate-specific membrane antigen ferroptosis

Identifiers

PMID35706368
PMCPMC9395313
OpenAlexW4282980090

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.