Evidence map›Paper›PMID 35995414›Full record

ArticleJournal of advanced research2023

Rapid generation of a mouse model for evaluating on-target normal tissue toxicity of human CAR-T cells using replication-defective recombinant adenovirus.

Qibin Liao, Zhuoqun Liu, Cuisong Zhu, Huan He, Meiqi Feng, Lang Jiang, Xiangqing Ding, Rongxun Sun, Xiaoyan Zhang, Jianqing Xu

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

Article in Journal of advanced research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.3field-weighted citation impact, top 41% 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

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. 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

10 authors at 4 institutions in 1 country.

Qibin LiaoZhongshan Hospital, Institutes of Biomedical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China; Department of Oncology and Bio-therapeutic Center, Shenzhen Third People's Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China.
Zhuoqun LiuZhongshan Hospital, Institutes of Biomedical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Cuisong ZhuZhongshan Hospital, Institutes of Biomedical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Huan HeZhongshan Hospital, Institutes of Biomedical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Meiqi FengZhongshan Hospital, Institutes of Biomedical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Lang JiangZhongshan Hospital, Institutes of Biomedical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Xiangqing DingZhongshan Hospital, Institutes of Biomedical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Rongxun SunDepartment of General Surgery, Jinshan Hospital of Fudan University, Shanghai, China. Electronic address: srongxun@hotmail.com.
Xiaoyan ZhangZhongshan Hospital, Institutes of Biomedical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. Electronic address: zhangxiaoyan@fudan.edu.cn.
Jianqing XuZhongshan Hospital, Institutes of Biomedical Sciences and Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. Electronic address: xujianqing@fudan.edu.cn.
Shanghai Public Health Clinical Center · CNZhongshan Hospital · CNJinshan Hospital of Fudan University · CNShenzhen Third People’s Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionThe on-target off-tumor toxicity of chimeric antigen receptor-engineered T cells (CAR-T) might lead to fatal side effects in cancer patients, which remains as a major obstacle to the clinical application of CAR-T immunotherapy. The off-tumor on-target normal tissue toxicity of CAR-T cells needs to be evaluated in preclinical studies using rational animal models.

objectivesWe aim to develop a rational animal model for assessing the off-tumor on-target normal tissue toxicity of various CAR-T cell designs quickly.

methodsWe used a recombinant adenovirus type 5 carrying human HER2/ERBB2 (Ad5-HER2) or CD47 gene (Ad5-CD47) to rapidly generate a mouse model with tunable human antigen expression on normal liver tissue to determine immunotoxicity of traditional CAR-T and hypoxia-response CAR-T cells in vivo.

resultsThe obvious liver damage and lymphocyte infiltration were not observed in mice with human antigen-high livers 8 days post-infection. Interestingly, the lethal liver damage, systemic cytokine release and CAR-T cells infiltration in liver were only observed in mice that received traditional CAR-T cells, but not in hypoxia-response CAR-T cells.

conclusionAdenovirus-based expression of target antigen in normal mouse tissue may be a useful method for assessing on-target CAR-T cell toxicity in normal tissues, especially various CAR-T cell designs that have the potency of conditional regulation in tumor microenvironment (TME).

Indexed as

NeoplasmsReceptors, Chimeric AntigenAdenoviridaeAnimalsCD47 AntigenHumansImmunotherapy, AdoptiveMiceT-LymphocytesTumor MicroenvironmentCD47 AntigenReceptors, Chimeric AntigenAdenovirusAnimal modelCAR-TNormal tissueOn-target off-tumor toxicity

Identifiers

PMID35995414
PMCPMC10173189
OpenAlexW4293040286

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.