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CAR T cell therapy for children with rheumatic disease: the time is now

Nature Reviews Rheumatology volume 21, pages 494–506 (2025)Cite this article

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Abstract

Initial success with B cell-targeted chimeric antigen receptor (CAR) T cells for the treatment of systemic lupus erythematosus and other rheumatic diseases has generated enthusiasm for the broad application of this technology outside of the field of oncology. Paediatric patients with severe rheumatic diseases require lifelong therapy with a substantial toxicity burden and a high cost of care. Paradigm-shifting treatments, including CAR T cells, are desperately needed. Although CAR T cell therapy shows promise for paediatric rheumatic diseases, there are unique aspects of care compared with adults, which require careful consideration and expertise. In response, we established the Integrated Multidisciplinary Paediatric Autoimmunity and Cell Therapy (IMPACT) working group, comprising international experts in the fields of paediatric rheumatology, oncology and cellular therapy, immunology and nephrology, to address the challenges of introducing cell therapies to patients with paediatric-onset autoimmune diseases. Given the possible benefits, we advocate for the study of CAR T cells in paediatric patients with rheumatic diseases who carry a lifelong risk of morbidity and mortality from chronic illness and medication toxicity. As this patient population is relatively small, consensus around definitions of success, robust study of predictors of response and uniform assessment and reporting of toxicities are critical to advancing the field.

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Fig. 1: The Integrated Multidisciplinary Paediatric Autoimmunity and Cell Therapy (IMPACT) working group.
Fig. 2: Paediatric-onset systemic lupus erythematosus as an example of the burden of paediatric-onset rheumatic disease.

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Author notes

  1. These authors contributed equally: Kaveh Ardalan, Margaret Lamb.

Authors and Affiliations

  1. Division of Immunology, Boston Children’s Hospital, Boston, MA, USA

    Holly Wobma

  2. Department of Paediatrics, Division of Rheumatology, Ohio State University, Columbus, OH, USA

    Stacy P. Ardoin, Kyla Driest & Ivana Stojkic

  3. Nationwide Children’s Hospital, Columbus, OH, USA

    Stacy P. Ardoin, Kyla Driest & Ivana Stojkic

  4. The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Challice L. Bonifant

  5. Department of Paediatrics, Section of Rheumatology, University of Colorado School of Medicine, Children’s Hospital Colorado, Aurora, CO, USA

    Jennifer C. Cooper

  6. Juvenile Myositis Pathogenesis and Therapeutics Unit, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA

    Hanna Kim

  7. Departments of Medicine and Paediatrics (Rheumatology), Duke University School of Medicine, Durham, NC, USA

    Rebecca E. Sadun

  8. Lupus Genomics and Global Health Disparities Unit, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA

    Laura Lewandowski

  9. Center for Cancer and Immunology Research and Division of Allergy and Immunology, Children’s National Hospital, Washington, DC, USA

    Michael Keller

  10. GW Cancer Center, George Washington University School of Medicine, Washington, DC, USA

    Michael Keller

  11. Paediatric Translational Research Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA

    Robert A. Colbert

  12. Departments of Internal Medicine and Paediatrics, Sections of Rheumatology and Paediatric Rheumatology, University of Chicago Medicine, Chicago, IL, USA

    Cuoghi Edens

  13. Department of Medicine, Division of Rheumatology, University of Pennsylvania, Philadelphia, PA, USA

    Kimberly DeQuattro

  14. Department of Paediatrics, Division of Paediatric Allergy, Immunology and Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Julia Shalen

  15. Division of Rheumatology, Hospital for Sick Children, Department of Paediatrics, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada

    Andrea Knight

  16. Department of Paediatrics, Division of Paediatric Oncology, University of Washington, Seattle, WA, USA

    Colleen Annesley

  17. Seattle Children’s Therapeutics, Seattle Children’s Hospital, Seattle, WA, USA

    Colleen Annesley

  18. Department of Paediatrics, Division of Rheumatology, University of Pittsburgh Medical Center, Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA

    Kathryn S. Torok

  19. Division of Oncology, Cellular Therapy and Transplantation Section, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Caitlin W. Elgarten

  20. Center for Cancer and Blood Disorders, Phoenix Children’s Hospital, Phoenix, AZ, USA

    Toshihiro Onishi

  21. Seattle Children’s Research Institute, Seattle, WA, USA

    Shaun W. Jackson

  22. Department of Paediatrics, University of Washington School of Medicine, Seattle, WA, USA

    Shaun W. Jackson

  23. Dana Farber Cancer Institute/Boston Children’s Hospital Center for Cancer and Blood Disorders, Boston, MA, USA

    Susan Prockop

  24. Paediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Nirali N. Shah

  25. Department of Paediatrics, Division of Paediatric Rheumatology, Duke University School of Medicine, Durham, NC, USA

    Kaveh Ardalan

  26. Department of Paediatrics, Division of Hematology, Oncology, Blood and Marrow Transplant, The Ohio State University, Nationwide Children’s Hospital, Columbus, OH, USA

    Margaret Lamb & Alexander Rankin

  27. Division of Rheumatology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Jon Burnham & Rebecca Scobell

  28. The University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    Jon Burnham

  29. Department of Paediatrics, University of Utah, Salt Lake City, UT, USA

    Aimee Hersh

  30. Department of Immunology and Microbiology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

    Elena Hsieh

  31. Section of Paediatric Allergy and Immunology, Department of Paediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Children’s Hospital Colorado, Aurora, CO, USA

    Elena Hsieh

  32. Division of Allergy Immunology and Rheumatology, Department of Paediatrics, Children’s Hospital of Michigan, Central Michigan University, Detroit, MI, USA

    Ryan Mitacek

  33. Division of Nephrology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Rebecca Scobell

  34. Division of Rheumatology, Department of Paediatrics, Comer Children’s Hospital, Chicago, IL, USA

    Melissa Tesher

  35. The Pritzker School of Medicine of the University of Chicago, Chicago, IL, USA

    Melissa Tesher

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  1. Holly Wobma
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  2. Stacy P. Ardoin
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  8. Michael Keller
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  9. Robert A. Colbert
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  10. Cuoghi Edens
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  11. Kimberly DeQuattro
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  13. Julia Shalen
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  14. Ivana Stojkic
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  15. Andrea Knight
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  16. Colleen Annesley
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  17. Kathryn S. Torok
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  18. Caitlin W. Elgarten
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  19. Toshihiro Onishi
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  20. Shaun W. Jackson
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  21. Susan Prockop
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  22. Nirali N. Shah
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  23. Kaveh Ardalan
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  24. Margaret Lamb
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Consortia

on behalf of the Integrated Multidisciplinary Paediatric Autoimmunity and Cell Therapy (IMPACT) working group*

  • Colleen Annesley
  • , Kaveh Ardalan
  • , Stacy P. Ardoin
  • , Challice L. Bonifant
  • , Jon Burnham
  • , Robert A. Colbert
  • , Jennifer C. Cooper
  • , Kimberly DeQuattro
  • , Kyla Driest
  • , Cuoghi Edens
  • , Caitlin W. Elgarten
  • , Aimee Hersh
  • , Elena Hsieh
  • , Shaun W. Jackson
  • , Hanna Kim
  • , Michael Keller
  • , Andrea Knight
  • , Margaret Lamb
  • , Laura Lewandowski
  • , Ryan Mitacek
  • , Toshihiro Onishi
  • , Susan Prockop
  • , Alexander Rankin
  • , Rebecca E. Sadun
  • , Rebecca Scobell
  • , Nirali N. Shah
  • , Julia Shalen
  • , Ivana Stojkic
  • , Melissa Tesher
  • , Kathryn S. Torok
  •  & Holly Wobma

Contributions

S.P., K.A., H.K., S.W.J., J.C.C., S.P.A., H.W., C.L.B, N.N.S. and M.L. researched data for the article and wrote the manuscript. All authors contributed substantially to discussion of the content and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Margaret Lamb.

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Competing interests

H.W. has stock ownership in Regatta Bio and has pending patent applications related to cellular therapies. C.L.B. has awarded and pending patent applications describing the use of engineered cells as therapeutics and has received research support from Merck, Sharp and Dohme, Bristol-Myers Squibb and Kiadis Pharma. J.C.C. is a consultant at Sana Biotechnology and Synthekine and is a Paediatric SLE Advisory Board Member for Bristol-Myers Squibb. H.K. is supported by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Arthritis and Musculoskeletal and Skin diseases (NIAMS) (AR041215), is a juvenile myositis expert panel member for Cabaletta Bio and is part of NIAMS CRADA with provision of a drug (deucravacitinib) with Bristol-Myers Squibb, and previously part of NIAMS CRADA, with study support and the drug (baricitinib) with Eli Lilly and Company. L.L is supported by ZIA AR04121404. M.K. receives author royalties from Wolter-Kluwer (UpToDate) and is a consultant for Chiesi Pharmaceuticals and M3 Global Research. R.A.C. is supported by ZIAAR041184. C.E. is a site PI of the Cabaletta Bio-sponsored RESET-SLE CAR T cell trial for SLE. S.W.J. is a consultant for Merck, IgM BioSciences and Sail BioMedicines and previously served as a consultant for Bristol-Myers Squib, Variant Bio and ChemoCentryx. S.W.J. has funding provided by the National Institutes of Health (1R01DK136980 and 1K24AR085177) and Lupus Research Alliance (Lupus Mechanisms and Targets Award and Global Team Science Award). S.P. receives support for the conducting of clinical trials through Boston Children’s Hospital from Atara and Jasper, is the inventor of IP related to development of third-party viral specific T cells programme with all rights assigned to Memorial Sloan Kettering Cancer Center, has received honoraria from Pierre Fabre, has engaged in consulting with Atara Biotherapeutics, Ensomo, HEOR, Pierre Fabre and VOR, is a DSMB member for Stanford University and NYBC and has equity interest in Regatta Biotherapies. N.N.S. receives research funding from Lentigen, VOR Bio and CARGO Therapeutics, has attended advisory board meetings (no honoraria) for VOR, ImmunoACT, and Sobi, receives royalties from CARGO and funding that supports this work was provided in part by the Intramural Research Program, Center of Cancer Research, National Cancer Institute and NIH Clinical Center, National Institutes of Health (ZIA BC 011823, N.N.S). K.A. has served on a scientific advisory board of Cabaletta Bio, completed paid consulting for Cabaletta Bio, serves as site PI of the Cabaletta Bio sponsored RESET-Myositis trial, serves as the Vice Chair of the Juvenile Dermatomyositis Committee for the Childhood Arthritis & Rheumatology Research Alliance (paid consultant position), has received honoraria/travel reimbursement from the Rheumatology Research Foundation and the American College of Rheumatology and receives research funding from the Rheumatology Research Foundation, Childhood Arthritis & Rheumatology Research Alliance/Arthritis Foundation, Chan Zuckerberg Initiative, Cure JM Foundation, Patient-Centered Outcomes Research Institute, and National Institutes of Health/Technical Resources International. M.L. participates in sponsored research funded by Luminary Biotherapeutics. The Integrated Multidisciplinary Paediatric Autoimmunity and Cell Therapy (IMPACT) Working Group has no competing interests to disclose. The remaining authors do not have any competing interests to disclose. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services or the National Institutes of Health, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

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Wobma, H., Ardoin, S.P., Bonifant, C.L. et al. CAR T cell therapy for children with rheumatic disease: the time is now. Nat Rev Rheumatol 21, 494–506 (2025). https://doi.org/10.1038/s41584-025-01272-3

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