Evidence map›Paper›PMID 36167591›Full record

ArticleJournal of translational medicine2022

Co-expression IL-15 receptor alpha with IL-15 reduces toxicity via limiting IL-15 systemic exposure during CAR-T immunotherapy.

Ying Zhang, Qinghui Zhuang, Fang Wang, Can Zhang, Chang Xu, Aiqin Gu, William H Zhong, Yi Hu, Xiaosong Zhong

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

Article in Journal of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
4.3field-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

37 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
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  6. Article
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  8. Article
  9. Article
  10. Article
  11. Syngeneic CAR T cells engineered for persistent delivery of desired proteins.Journal of controlled release : official journal of the Controlled Release Society · 2025
    Article
  12. Article
  13. Cell-Based Therapies for Solid Tumors: Challenges and Advances.International journal of molecular sciences · 2025
    Review
  14. Review
  15. Presetting CAR-T cells during ex vivo biomanufacturing.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Review
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 2 institutions in 1 country.

Ying Zhang *The Clinical Center of Gene and Cell Engineering, Beijing Shijitan Hospital, Capital Medical University, Haidian District, No. 10, Iron Medicine Road, Yang Fang Dian, Beijing, 100038, China.
Qinghui Zhuang *The Clinical Center of Gene and Cell Engineering, Beijing Shijitan Hospital, Capital Medical University, Haidian District, No. 10, Iron Medicine Road, Yang Fang Dian, Beijing, 100038, China.
Fang WangThe Clinical Center of Gene and Cell Engineering, Beijing Shijitan Hospital, Capital Medical University, Haidian District, No. 10, Iron Medicine Road, Yang Fang Dian, Beijing, 100038, China.
Can ZhangThe Clinical Center of Gene and Cell Engineering, Beijing Shijitan Hospital, Capital Medical University, Haidian District, No. 10, Iron Medicine Road, Yang Fang Dian, Beijing, 100038, China.
Chang XuThe Clinical Center of Gene and Cell Engineering, Beijing Shijitan Hospital, Capital Medical University, Haidian District, No. 10, Iron Medicine Road, Yang Fang Dian, Beijing, 100038, China.
Aiqin GuThe Clinical Center of Gene and Cell Engineering, Beijing Shijitan Hospital, Capital Medical University, Haidian District, No. 10, Iron Medicine Road, Yang Fang Dian, Beijing, 100038, China.
William H Zhong, River Hill High School, Clarksville, MD, USA.
Yi HuThe Clinical Center of Gene and Cell Engineering, Beijing Shijitan Hospital, Capital Medical University, Haidian District, No. 10, Iron Medicine Road, Yang Fang Dian, Beijing, 100038, China.
Xiaosong ZhongThe Clinical Center of Gene and Cell Engineering, Beijing Shijitan Hospital, Capital Medical University, Haidian District, No. 10, Iron Medicine Road, Yang Fang Dian, Beijing, 100038, China. zhongxiaosong7113@bjsjth.cn.
Beijing Shijitan Hospital · CNCapital Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChimeric antigen receptor (CAR)-T cell therapy is a powerful adoptive immunotherapy against both B-cell malignancies and some types of solid tumors. Interleukin (IL) -15 is an important immune stimulator that may provide ideal long-term persistent CAR-T cells. However, higher base line or peak serum IL-15 levels are also related to severe toxicity, such as cytokine release syndrome (CRS), graft-versus-host disease (GVHD), and neurotoxicity.

methodsWe successfully constructed CD19 specific armored CAR-T cells overexpressing IL-I5 and IL-15 receptor alpha (IL-15Ra). In vitro cell differentiation and viability were monitored by flow cytometry, and an in vivo xenograft mouse models was used to evaluate the anti-tumor efficiency and liver damage of CAR-T cells.

resultsCAR-T cells overexpressing IL-15 alone demonstrated enhanced viability, retarded exhaustion in vitro and superior tumor-inhibitory effects in vivo. However, these tumor-free mice had lower survival rates, with serious liver injuries, as a possible result of toxicity. As expected, CAR-T cells overexpressing IL-15 combined with IL-15Ra had reduced CD132 expression and released fewer cytokines (IFNγ, IL-2 and IL-15) in vitro, as well as had the tendency to improve mouse survival via repressing the growth of tumor cells and keeping livers healthier compared to CAR-IL-15 T cells.

conclusionsThese results indicated the importance of IL-15 in enhancing T cells persistence and IL-15Ra in reducing the adverse effects of IL-15, with superior tumor retardation during CAR-T therapy. This study paves the way for the rapid exploitation of IL-15 in adoptive cell therapy in the future.

Indexed as

NeoplasmsReceptors, Chimeric AntigenAnimalsCytokinesHumansImmunotherapyImmunotherapy, AdoptiveInterleukin-15Interleukin-15 Receptor alpha SubunitInterleukin-2MiceCytokinesInterleukin-15Interleukin-15 Receptor alpha SubunitInterleukin-2Receptors, Chimeric AntigenArmored chimeric antigen receptor TInterleukin 15Interleukin 15 receptor alphaToxicity

Identifiers

PMID36167591
PMCPMC9516829
OpenAlexW4297380470

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.