Evidence map›Paper›PMID 37917882›Full record

ArticleJCI insight2023

A CD6-targeted antibody-drug conjugate as a potential therapy for T cell-mediated disorders.

Lingjun Zhang, Liping Luo, Jin Y Chen, Rupesh Singh, William M Baldwin, David A Fox, Daniel J Lindner, Daniel F Martin, Rachel R Caspi, Feng Lin

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
3.2field-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

6 citing papers in PubMed, 14 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

10 authors at 3 institutions in 1 country.

Lingjun ZhangDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland, Ohio, USA.
Liping LuoDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland, Ohio, USA.
Jin Y ChenDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland, Ohio, USA.
Rupesh SinghCole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA.
William M BaldwinDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland, Ohio, USA.
David A FoxDivision of Rheumatology and Clinical Autoimmunity Center of Excellence, University of Michigan, Ann Arbor, Michigan, USA.
Daniel J LindnerDepartment of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Daniel F MartinCole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Rachel R CaspiLaboratory of Immunology, National Eye Institute, NIH, Bethesda, Maryland, USA.
Feng LinDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland, Ohio, USA.
Cleveland Clinic · USNational Eye Institute · USUniversity of Michigan · US

Funding

Autoimmunity Center of Excellence Clinical Research ProgramUM1AI110498 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WOFSY, DAVID · 2014 to 2019
$31.4M
The Cleveland Clinic Innovation AcceleratorU54HL119810 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI VINCE, D. GEOFFREY · 2013 to 2020
$14.4M
Role of CDCP1 in the pathogenesis of autoimmune uveitisR01EY034077 · NEI · CLEVELAND CLINIC LERNER COM-CWRU · PI FENG C LIN · 2023 to 2026
$2.0M
Role of CD6 in the pathogenesis of autoimmune uveitisR01EY025373 · NEI · CLEVELAND CLINIC LERNER COM-CWRU · PI LIN, FENG C · 2017 to 2021
$2.0M
A novel regulator of corneal wound healing and Pseudomonas aeruginosa keratitisR01EY030111 · NEI · CLEVELAND CLINIC LERNER COM-CWRU · PI LIN, FENG C, TAM, K. P. CONNIE · 2019 to 2022
$1.6M
University of Michigan Clinical Autoimmunity Center of ExcellenceUM1AI144298 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FOX, DAVID ALAN, KHANNA, DINESH · 2019 to 2023
$546k
Development of a novel antibody-drug conjugate for treating T-cell lymphoma.R41CA275639 · NCI · ABCON THERAPEUTICS, INC. · PI LIN, FENG C · 2022 to 2022
$403k
Immunotherapy of prostate cancer using an anti-CD6 monoclonal antibodyR21CA287325 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FOX, DAVID ALAN · 2024 to 2025
$401k
Development of new models of AMDR21EY031087 · NEI · CLEVELAND CLINIC LERNER COM-CWRU · PI LIN, FENG C · 2019 to 2019
$348k
Development of a new drug for treating autoimmune uveitisR41EY033243 · NEI · ABCON THERAPEUTICS, INC. · PI LIN, FENG C · 2021 to 2021
$255k
NCI NIH HHS R21 CA287325NEI NIH HHS R01 EY025373NEI NIH HHS R01 EY030111NEI NIH HHS R01 EY034077NEI NIH HHS R21 EY031087NEI NIH HHS R41 EY033243NHLBI NIH HHS U54 HL119810NIAID NIH HHS UM1 AI110498NIAID NIH HHS UM1 AI144298
6 · The paper itself

Abstract

The selective targeting of pathogenic T cells is a holy grail in the development of new therapeutics for T cell-mediated disorders, including many autoimmune diseases and graft versus host disease. We describe the development of a CD6-targeted antibody-drug conjugate (CD6-ADC) by conjugating an inactive form of monomethyl auristatin E (MMAE), a potent mitotic toxin, onto a mAb against CD6, an established T cell surface marker. Even though CD6 is present on all T cells, only the activated (pathogenic) T cells vigorously divide and thus are susceptible to the antimitotic MMAE-mediated killing via the CD6-ADC. We found CD6-ADC selectively killed activated proliferating human T cells and antigen-specific mouse T cells in vitro. Furthermore, in vivo, whereas the CD6-ADC had no significant detrimental effect on normal T cells in naive CD6-humanized mice, the same dose of CD6-ADC, but not the controls, efficiently treated 2 preclinical models of autoimmune uveitis and a model of graft versus host disease. These results provide evidence suggesting that CD6-ADC could be further developed as a potential therapeutic agent for the selective elimination of pathogenic T cells and treatment of many T cell-mediated disorders.

Indexed as

Autoimmune DiseasesGraft vs Host DiseaseImmunoconjugatesAnimalsCD3 ComplexHumansMiceT-LymphocytesCD3 ComplexImmunoconjugatesAutoimmunityT cells

Identifiers

PMID37917882
PMCPMC10795824
OpenAlexW4388212342

What OpenQuestion holds

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LicenceCC BY
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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.