Evidence map›Paper›PMID 38610029›Full record

ArticleJournal of translational medicine2024

Development of nanobodies targeting hepatocellular carcinoma and application of nanobody-based CAR-T technology.

Keming Lin, Baijin Xia, Xuemei Wang, Xin He, Mo Zhou, Yingtong Lin, Yidan Qiao, Rong Li, Qier Chen, Yuzhuang Li and 8 more

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 7% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
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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

18 authors at 1 institution in 1 country.

Keming LinInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou, Guangdong, 510080, People's Republic of China.
Baijin XiaInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou, Guangdong, 510080, People's Republic of China.
Xuemei WangInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou, Guangdong, 510080, People's Republic of China.
Xin HeInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou, Guangdong, 510080, People's Republic of China.
Mo ZhouInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou, Guangdong, 510080, People's Republic of China.
Yingtong LinInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou, Guangdong, 510080, People's Republic of China.
Yidan QiaoInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou, Guangdong, 510080, People's Republic of China.
Rong LiInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou, Guangdong, 510080, People's Republic of China.
Qier ChenInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou, Guangdong, 510080, People's Republic of China.
Yuzhuang LiInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou, Guangdong, 510080, People's Republic of China.
Jinzhu FengInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou, Guangdong, 510080, People's Republic of China.
Tao ChenInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou, Guangdong, 510080, People's Republic of China.
Cancan ChenDepartment of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
Xinyu LiShenzhen Key Laboratory of Systems Medicine for Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, People's Republic of China.
Hui ZhangInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou, Guangdong, 510080, People's Republic of China.
Lijuan LuDepartment of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Avenue, Guangzhou, Guangdong, 510630, People's Republic of China. lulj25@mail.sysu.edu.cn.
Bingfeng LiuInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou, Guangdong, 510080, People's Republic of China. liubf5@mail.sysu.edu.cn.ORCID 0000-0003-1278-727X
Xu ZhangInstitute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, No. 74 Zhongshan Road 2, Yuexiu District, Guangzhou, Guangdong, 510080, People's Republic of China. zhxu22@mail.sysu.edu.cn.
Sun Yat-sen University · CN

Funding

Basic and Applied Basic Research Fund Committee of Guangdong Province SL2022A04J01923Emergency Key Program of Guangzhou National Laboratory EKPG21-24Exchange Program of NSFC 82150710553Guangdong Basic and Applied Basic Research Foundation 2023A1515010476Guangzhou Science and technology plan project 2023A04J2235Important Key Program of Natural Science Foundation of China (NSFC) 92169201Key R&D Program of Department of Science and Technology of Guangdong 2022B1111020004National Key R&D Program of Department of Science and Technology of China 2022YFC0870700National key research and development program 2021YFC2301904National Natural Science Foundation of China 82202036
6 · The paper itself

Abstract

backgroundChimeric antigen receptor T (CAR-T) cell therapy, as an emerging anti-tumor treatment, has garnered extensive attention in the study of targeted therapy of multiple tumor-associated antigens in hepatocellular carcinoma (HCC). However, the suppressive microenvironment and individual heterogeneity results in downregulation of these antigens in certain patients' cancer cells. Therefore, optimizing CAR-T cell therapy for HCC is imperative.

methodsIn this study, we administered FGFR4-ferritin (FGFR4-HPF) nanoparticles to the alpaca and constructed a phage library of nanobodies (Nbs) derived from alpaca, following which we screened for Nbs targeting FGFR4. Then, we conducted the functional validation of Nbs. Furthermore, we developed Nb-derived CAR-T cells and evaluated their anti-tumor ability against HCC through in vitro and in vivo validation.

resultsOur findings demonstrated that we successfully obtained high specificity and high affinity Nbs targeting FGFR4 after screening. And the specificity of Nbs targeting FGFR4 was markedly superior to their binding to other members of the FGFR family proteins. Furthermore, the Nb-derived CAR-T cells, targeting FGFR4, exhibited significantly enhanced anti-tumor efficacy in both experiments when in vitro and in vivo.

conclusionsIn summary, the results of this study suggest that the CAR-T cells derived from high specificity and high affinity Nbs, targeting FGFR4, exhibited significantly enhanced anti-tumor efficacy in vitro and in vivo. This is an exploration of FGFR4 in the field of Nb-derived CAR-T cell therapy for HCC, holding promise for enhancing safety and effectiveness in the clinical treatment of HCC in the future.

Indexed as

Camelids, New WorldCarcinoma, HepatocellularLiver NeoplasmsReceptors, Chimeric AntigenSingle-Domain AntibodiesAnimalsHumansTumor MicroenvironmentReceptors, Chimeric AntigenSingle-Domain AntibodiesHCCNanobodyNanoparticleNb-derived CAR-T cell therapyPhage display

Identifiers

PMID38610029
PMCPMC11015683
OpenAlexW4394766426

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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.