Evidence map›Paper›PMID 34897774›Full record

ArticleHepatology (Baltimore, Md.)2022

Novel low-avidity glypican-3 specific CARTs resist exhaustion and mediate durable antitumor effects against HCC.

Leidy D Caraballo Galva, Xiaotao Jiang, Mohamed S Hussein, Huajun Zhang, Rui Mao, Pierce Brody, Yibing Peng, Aiwu Ruth He, Mercy Kehinde-Ige, Ramses Sadek and 3 more

Open access · greenAbstract read
In one paragraph

Article in Hepatology (Baltimore, Md.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.1field-weighted citation impact, top 10% 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

19 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
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  6. Engineering resilient CAR T cells for immunosuppressive environment.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    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

13 authors at 3 institutions in 2 countries.

Leidy D Caraballo GalvaGeorgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.ORCID 0000-0003-4263-8419
Xiaotao JiangGeorgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.ORCID 0000-0001-7571-1593
Mohamed S HusseinGeorgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.ORCID 0000-0001-9277-713X
Huajun ZhangDepartment of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada.
Rui MaoGeorgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.
Pierce BrodyGeorgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.
Yibing PengGeorgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.
Aiwu Ruth HeLombardi Cancer Center, Georgetown University, Washington, District of Columbia, USA.
Mercy Kehinde-IgeGeorgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.
Ramses SadekGeorgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.
Xiangguo QiuDepartment of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada.
Huidong ShiGeorgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.ORCID 0000-0003-1137-3390
Yukai HeGeorgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.ORCID 0000-0001-7636-5549
Augusta University · USUniversity of Manitoba · CAGeorgetown University · US

Funding

TCR engineering of human T cells for immunotherapy of hepatocellular carcinomaR01CA235159 · NCI · AUGUSTA UNIVERSITY · PI HE, YUKAI · 2019 to 2024
$1.9M
NCI NIH HHS R01 CA235159
6 · The paper itself

Abstract

BACKGROUND AND

aimsChimeric antigen receptor engineered T cells (CARTs) for HCC and other solid tumors are not as effective as they are for blood cancers. CARTs may lose function inside tumors due to persistent antigen engagement. The aims of this study are to develop low-affinity monoclonal antibodies (mAbs) and low-avidity CARTs for HCC and to test the hypothesis that low-avidity CARTs can resist exhaustion and maintain functions in solid tumors, generating durable antitumor effects. METHODS AND

resultsNew human glypican-3 (hGPC3) mAbs were developed from immunized mice. We obtained three hGPC3-specific mAbs that stained HCC tumors, but not the adjacent normal liver tissues. One of them, 8F8, bound an epitope close to that of GC33, the frequently used high-affinity mAb, but with approximately 17-fold lower affinity. We then compared the 8F8 CARTs to GC33 CARTs for their in vitro function and in vivo antitumor effects. In vitro, low-avidity 8F8 CARTs killed both hGPC3

conclusionThe low-avidity 8F8-BBz CART resists exhaustion and apoptosis inside tumor lesions, demonstrating a greater therapeutic potential than high-avidity CARTs.

Indexed as

Carcinoma, HepatocellularLiver NeoplasmsAnimalsAntibodies, MonoclonalGlypicansHumansMiceXenograft Model Antitumor AssaysAntibodies, MonoclonalGlypicans

Identifiers

PMID34897774
PMCPMC10568540
OpenAlexW4200266275

What OpenQuestion holds

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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.