Evidence map›Paper›PMID 41279526›Full record

ArticlebioRxiv : the preprint server for biology2025

Precision targeting of autoreactive B cells in systemic lupus erythematosus using anti-9G4 idiotope synthetic immune receptor T cells.

Jin Liu, Yuanxuan Xia, Brian J Mog, Colin Gliech, Elana Shaw, Dylan Ferris, Brock Moritz, Tolulope O Awosika, Sarah R DiNapoli, Stephanie Glavaris and 18 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

28 authors.

Jin LiuDivision of Rheumatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Yuanxuan XiaDivision of Rheumatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Brian J MogLudwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Colin GliechDivision of Rheumatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Elana ShawDivision of Rheumatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Dylan FerrisDivision of Rheumatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Brock MoritzDivision of Rheumatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Tolulope O AwosikaLudwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sarah R DiNapoliLudwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Stephanie GlavarisLudwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kyle J KaeoDivision of Rheumatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Xuyang LiLudwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nikita MarcouLudwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Alexander H PearlmanLudwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Taha S AhmednaLudwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Regina BugrovskyEmory University School of Medicine, Atlanta, GA, USA.
Iñaki SanzEmory University School of Medicine, Atlanta, GA, USA.
Chetan BettegowdaLudwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Suman PaulLudwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Victoria Duarte AlvaradoJohns Hopkins Institute for Nanobiotechnology, The Johns Hopkins University, Baltimore, MD, USA.
Denis WirtzDepartment of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Daniel GoldmanDivision of Rheumatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Michelle PetriDivision of Rheumatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kenneth W KinzlerLudwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Shibin ZhouLudwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Felipe AndradeDivision of Rheumatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Bert VogelsteinLudwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Maximilian F KonigDivision of Rheumatology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0003-3415-0704

Funding

MULTIDISCIPLINARY TRAINING PROGRAM IN LUNG DISEASEST32HL007534 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI Nadia N Hansel, Larissa A. Shimoda · 1985 to 2026
$28.3M
Medical Scientist Training ProgramT32GM136577 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI ANDREA L COX · 2020 to 2026
$13.4M
Tech Core 2U54CA268083 · NCI · JOHNS HOPKINS UNIVERSITY · PI Denis Wirtz · 2022 to 2026
$10.2M
Interrogating malignant gliomas using released tumor DNA in cerebrospinal fluidR37CA230400 · NCI · JOHNS HOPKINS UNIVERSITY · PI BETTEGOWDA, CHETAN · 2018 to 2024
$2.6M
Engineering self-propelled tumor-infiltrating CAR T cells using synthetic velocity receptorsR01CA300052 · NCI · JOHNS HOPKINS UNIVERSITY · PI Denis Wirtz · 2025 to 2026
$1.3M
Three-dimensional maps of senescence in the human pancreasUG3CA275681 · NCI · JOHNS HOPKINS UNIVERSITY · PI WU, PEI-HSUN · 2022 to 2023
$1.1M
TCR Targeting Antibodies for the Treatment of T cell CancersK08CA270403 · NCI · JOHNS HOPKINS UNIVERSITY · PI Suman Paul · 2022 to 2026
$1.1M
Precision immunotherapies targeting the 9G4 idiotype in lupus erythematosusR21AI176764 · NIAID · JOHNS HOPKINS UNIVERSITY · PI ANDRADE, FELIPE, KONIG, MAXIMILIAN FERDINAND · 2023 to 2024
$450k
The antigenic origin of anti-dsDNA antibodies in SLER21AI183329 · NIAID · JOHNS HOPKINS UNIVERSITY · PI ANDRADE, FELIPE · 2024 to 2025
$444k
NCI NIH HHS K08 CA270403NCI NIH HHS R01 CA300052NCI NIH HHS R37 CA230400NCI NIH HHS U54 CA268083NCI NIH HHS UG3 CA275681NHLBI NIH HHS T32 HL007534NIAID NIH HHS R21 AI176764NIAID NIH HHS R21 AI183329NIGMS NIH HHS T32 GM136577
6 · The paper itself

Abstract

Chimeric antigen receptor (CAR)-T cell therapies that broadly target B cells can achieve complete remission in severe systemic lupus erythematosus (SLE) but carry an increased risk of infection and cytokine-related toxicities that limit their use. Alternative strategies that combine the potency of immune effector cell therapies with more precise targeting approaches have the potential to control disease without the challenges of broad immunosuppression. B cells expressing immunoglobulin heavy variable gene 4-34 (IGHV4-34)-derived B cell receptors (BCRs) are a major source of disease-relevant autoantibodies in lupus and other autoimmune diseases. Here, we exploit a common feature of IGHV4-34 BCRs, namely the 9G4 idiotope (9G4id), to develop precision cellular immunotherapies that target autoreactive B cells. Anti-9G4 CAR-T cells and anti-9G4 chimeric T cell receptor (cTCR) T cells, integrating anti-9G4 antibody fragments into a re-engineered TCR scaffold, eliminated autoreactive Ramos B cells expressing SLE patient-derived 9G4id BCRs with equal potency, while sparing non-9G4 Ramos B cells. Using SLE patient PBMCs, autologous anti-9G4 cTCR-T cells and anti-9G4 CAR-T cells selectively depleted primary human 9G4id B cells, while maintaining total B cell numbers. Similarly, anti-9G4 T cells eliminated B cells expressing 9G4id BCRs from patients with cold agglutinin disease and Burkitt lymphoma. Compared to broad targeting with CD19 CAR-T cells, anti-9G4 T cell therapies showed lower cytokine release (~6-8-fold for interferon [IFN]-γ). In addition, anti-9G4 cTCR-T cells showed ~17-fold lower IFN-γ secretion compared to anti-9G4 CAR-T cells, despite achieving similar cytotoxicity. Together, our findings suggest that anti-9G4 precision cellular therapies provide a strategy to selectively target pathogenic B cells in SLE, while minimizing risks of infection and cytokine-related toxicities.

Indexed as

9G4 idiotopeautoimmunitychimeric antigen receptorchimeric T cell receptorimmune effector cell therapysystemic lupus erythematosusVH4-34

Identifiers

PMID41279526
PMCPMC12632787

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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.