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Review
. 2025 Oct 5;11(4):e005866.
doi: 10.1136/rmdopen-2025-005866.

Key considerations for advancing chimeric antigen receptor (CAR) T-cell therapy for systemic lupus erythematosus (SLE): a multi-partner/disciplinary working group perspective

Elena W Y Hsieh #  1 , James B Chung #  2 , Afsah Amin  3 , Anca D Askanase  4 , Beatrix Bartok  5 , Paul Brunetta  6 , Marlene J Carrasco-Alfonso  7 , Cindy Coney  8 , Jennifer C Cooper  9 , Maria Dall'Era  10 , Nikolay Delev  11 , Ann Eldred  12 , Richard A Furie  13 , Sandra Garces  11 , Katie Groover  14 , Monica Harrington  15 , Jonathan J Hogan  16 , Gavin H Imperato  3 , Meredith Jackson  17 , Shaun W Jackson  18 , Artemio M Jongco  19 , Elaine Karis  20 , Ashley Koegel  11 , Maximilian F König  21   22 , Gary Koretzky  23 , Vijay Kumar  3 , Eric Morand  24   25 , Aimee S Payne  4 , Vaishali Popat  26 , Naiyer Rizvi  27 , Patricia Rohan  28 , Michel Sadelain  4 , Georg Schett  29   30 , Aman P Singh  31 , Ronald F van Vollenhoven  32 , Debra Zack  33 ; Lupus ABC CAR T Working Group
Collaborators, Affiliations
Review

Key considerations for advancing chimeric antigen receptor (CAR) T-cell therapy for systemic lupus erythematosus (SLE): a multi-partner/disciplinary working group perspective

Elena W Y Hsieh et al. RMD Open. .

Abstract

Early data have shown the potential of chimeric antigen receptor (CAR) T-cell therapies to expand the therapeutic landscape in systemic lupus erythematosus (SLE). While many CAR T-cell therapy learnings can be drawn from the experience of this modality in oncology, key questions remain regarding clinical development considerations unique to lupus. To assess and discuss these issues, the Lupus Accelerating Breakthroughs Consortium, a public-private partnership, convened a multi-partner working group to collect the diverse perspectives of academics/clinicians (including rheumatologists and oncologists), industry representatives (including SLE as well as CAR T-cell clinical development experts), regulators and people living with lupus on this potentially ground-breaking therapy. The working group considered the risk/benefit considerations for eligibility criteria in lupus, early-phase dosing and dose-limiting toxicity challenges, incorporation of comparator arms in late-phase registrational trial design, SLE-specific issues in conditioning therapy and immune monitoring and the limitations of SLE pre-clinical models for studying cell therapies. The key future 'calls to action' for the field include the need for well-defined severity/refractoriness-based eligibility criteria, the need for long-term monitoring infrastructure and the need for educational and logistical support for rheumatologists and patients.

Keywords: Biological Therapy; Clinical Trial; Lupus Erythematosus, Systemic; Lupus Nephritis; T-Lymphocytes.

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Conflict of interest statement

Competing interests: J Chung was an employee of Kyverna Therapeutics from April 2021 to November 2024 and received stock options and other compensation. A Askanase has received grants or contracts from US DoD-CDMRP, HHS, Idorsia, Bristol Meyers Squibb (BMS), AstraZeneca, Cabaletta, UCB, Sanofi, Alumis and Nkarta and consulting fees from GSK, AstraZeneca and Novartis. A Askanase also discloses roles in the Lupus Foundation of America (Medical Scientific Advisory Council), Lupus Research Alliance (Medical Advisory Board), SLICC (Material Transfer Committee, Membership Committee) and American College of Rheumatology (Annual Meeting Planning Committee). P Brunetta is an employee and shareholder of Sana Biotechnology, Inc. M J Carrasco-Alfonso is an employee and shareholder of AstraZeneca. JC Cooper has received consulting fees from Sana Biotechnology, Synthekine and Bristol Myers Squibb. M Dall’Era has received consulting fees (individual payments and payments to institution) from Abelzeta, Fate Therapeutics, Artiva and BMS and has participated on a data safety monitoring board or advisory board for Novartis and Cabaletta. N Delev is an employee of BMS. A Eldred is an employee and shareholder of Abbvie. S Garces is a BMS employee and shareholder. M Harrington received financial support from the Lupus Research Alliance for drafting this manuscript. J Hogan is an employee and shareholder of Cabaletta Bio and also receives a yearly royalty from the University of Pennsylvania for the co-invention of chimeric autoantibody receptor (CAAR) T-cell therapy for PLA2R membranous nephropathy (and is named on the patent for this invention). SW Jackson received grant support from the Lupus Research Alliance and NIH for projects relevant to the subjects of this manuscript and consulting fees from BMS, Merck, Sail Biotherapeutics, IgM Bio, Chemocentryx and Variant Bio. A Jongco is an employee and shareholder of GlaxoSmithKline (GSK). E Karis is an employee of BMS and stockholder of Nkarta and Amgen Inc. A Koegel is an employee and stockholder of BMS and is named on patents planned issued or pending associated with BMS employment. M Konig has received grants or contracts from NIH/NIAMS, the Lupus Research Alliance, the Rheumatology Research Foundation, Harrington Discovery Institute, CureAAV and Blackbird Labs; royalties or licences from TBD Pharmaceuticals; consulting fees from Allogene, Argenx, Atara Biotherapeutics, BMS, Revel Pharmaceuticals and Sana Biotechnology; and payment or honoraria for lectures, writing or educational events at BMS and participated on a data safety monitoring board or advisory board for Allogene, Sana Biotechnology and TBD Pharmaceuticals, Inc. M Konig also holds stock options and a leadership or fiduciary role in a board associated with TBD Pharmaceuticals, Inc. E Morand has received research funding to employing institution from Abbvie, Amgen, AstraZeneca, biogen, BMS, Eli Lilly, Merck Serono, Genentech-Hoffman La Roche, GSK, Janssen, Novartis, Takeda and Union Chimique Belge; consulting fees from AstraZeneca, Biogen, BMS, Galapagos, Gilead, Genentech-Hoffman La Roche, GSK, Merck Serono, Novartis, Priovant, IgM, Janssen, Quell, Remegen, Takeda and Zenas; honoraria for lectures/symposia (and travel support) from AstraZeneca, Merck Serono and Novartis; patents related to the use of anifrolumab in treatment of SLE and use of antigen-specific TCR expressing regulatory T cells in the treatment of SLE (WO2021094378A1, WO2023057369A2, WO2021184080A1, WO2023044530A1 and WO2022074123A1 (pending)); participation as a Scientific Advisory Board member of Dragonfly Tx; and leadership or fiduciary roles in Rare Voices Australia (advocacy group) and Exosome Biosciences Pty Ltd (board director). A Payne has received grants or contracts, royalties or licenses and stock/options from Cabaletta Bio and consulting fees from Janssen, Sanofi, BMS and Avilar has served leadership roles in the Society for Investigative Dermatology (President), Advancing Innovation in Dermatology (Board of Trustees) and Cabaletta Bio (Scientific Advisory Board co-chair). M Sadelain has received grants or contracts from Takeda Pharmaceuticals, Fate Therapeutics, Atara Biotherapeutics and royalties or licenses from Juno Therapeutics/BMS pertaining to CAR-T cells used in oncology. G Schett has received payment or honoraria for speakers bureaus from Cabaletta, Novartis, Janssen and Kyverna Therapeutics. A Singh is an employee and shareholder of Takeda Pharmaceuticals. R van Vollenhoven has received grants or contracts from AstraZeneca, BMS, Cabaletta and Remegen; consulting fees from Abbvie, AstraZeneca, Biogen, BMS, Cabaletta, Galapagos, GSK, Janssen, Kyowakirin, Pfizer, RemeGen, Sanofi and UCB; and payment or honoraria for lectures from Abbvie, AstraZeneca, Biogen, BMS, Cabaletta, Galapagos, GSK, Janssen, Kyowakirin, Pfizer, RemeGen, Sanofi and UCB and participated on Data Safety Monitoring Board or Advisory Boards of AbbVie, AstraZeneca, Biogen, BMS, Cabaletta, Galapagos, GSK, Janssen, Kyowakirin, Pfizer, RemeGen, Sanofi and UCB. D Zack is a paid part-time consultant and receives consulting fees from Fate Therapeutics.

Figures

Figure 1
Figure 1. Key goals for advancing CAR T-cell therapy for lupus patients. CAR, chimeric antigen receptor; SLE, systemic lupus erythematosus.
See this image and copyright information in PMC

References

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