Review

. 2025 Aug;21(8):494-506.

doi: 10.1038/s41584-025-01272-3. Epub 2025 Jul 2.

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

Holly Wobma¹, Stacy P Ardoin^{2

3}, Challice L Bonifant⁴, Jennifer C Cooper⁵, Hanna Kim⁶, Rebecca E Sadun⁷, Laura Lewandowski⁸, Michael Keller^{9

10}, Robert A Colbert¹¹, Cuoghi Edens¹², Kimberly DeQuattro¹³, Kyla Driest^{2

3}, Julia Shalen¹⁴, Ivana Stojkic^{2

3}, Andrea Knight¹⁵, Colleen Annesley^{16

17}, Kathryn S Torok¹⁸, Caitlin W Elgarten¹⁹, Toshihiro Onishi²⁰, Shaun W Jackson^{21

22}, Susan Prockop²³, Nirali N Shah²⁴, Kaveh Ardalan^#²⁵, Margaret Lamb^#²⁶; Integrated Multidisciplinary Paediatric Autoimmunity and Cell Therapy (IMPACT) working group*

Collaborators, Affiliations

Collaborators

Integrated Multidisciplinary Paediatric Autoimmunity and Cell Therapy (IMPACT) working group*:
Jon Burnham, Aimee Hersh, Elena Hsieh, Ryan Mitacek, Alexander Rankin, Rebecca Scobell, Melissa Tesher

Affiliations

¹ Division of Immunology, Boston Children's Hospital, Boston, MA, USA.
² Department of Paediatrics, Division of Rheumatology, Ohio State University, Columbus, OH, USA.
³ Nationwide Children's Hospital, Columbus, OH, USA.
⁴ The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Department of Paediatrics, Section of Rheumatology, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO, USA.
⁶ Juvenile Myositis Pathogenesis and Therapeutics Unit, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
⁷ Departments of Medicine and Paediatrics (Rheumatology), Duke University School of Medicine, Durham, NC, USA.
⁸ Lupus Genomics and Global Health Disparities Unit, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
⁹ Center for Cancer and Immunology Research and Division of Allergy and Immunology, Children's National Hospital, Washington, DC, USA.
¹⁰ GW Cancer Center, George Washington University School of Medicine, Washington, DC, USA.
¹¹ Paediatric Translational Research Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
¹² Departments of Internal Medicine and Paediatrics, Sections of Rheumatology and Paediatric Rheumatology, University of Chicago Medicine, Chicago, IL, USA.
¹³ Department of Medicine, Division of Rheumatology, University of Pennsylvania, Philadelphia, PA, USA.
¹⁴ Department of Paediatrics, Division of Paediatric Allergy, Immunology and Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁵ Division of Rheumatology, Hospital for Sick Children, Department of Paediatrics, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada.
¹⁶ Department of Paediatrics, Division of Paediatric Oncology, University of Washington, Seattle, WA, USA.
¹⁷ Seattle Children's Therapeutics, Seattle Children's Hospital, Seattle, WA, USA.
¹⁸ Department of Paediatrics, Division of Rheumatology, University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
¹⁹ Division of Oncology, Cellular Therapy and Transplantation Section, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
²⁰ Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, AZ, USA.
²¹ Seattle Children's Research Institute, Seattle, WA, USA.
²² Department of Paediatrics, University of Washington School of Medicine, Seattle, WA, USA.
²³ Dana Farber Cancer Institute/Boston Children's Hospital Center for Cancer and Blood Disorders, Boston, MA, USA.
²⁴ Paediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
²⁵ Department of Paediatrics, Division of Paediatric Rheumatology, Duke University School of Medicine, Durham, NC, USA.
²⁶ Department of Paediatrics, Division of Hematology, Oncology, Blood and Marrow Transplant, The Ohio State University, Nationwide Children's Hospital, Columbus, OH, USA. margaret.lamb2@nationwidechildrens.org.

^# Contributed equally.

PMID: 40603629
DOI: 10.1038/s41584-025-01272-3

Review

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

Holly Wobma et al. Nat Rev Rheumatol. 2025 Aug.

. 2025 Aug;21(8):494-506.

doi: 10.1038/s41584-025-01272-3. Epub 2025 Jul 2.

Authors

Collaborators

Integrated Multidisciplinary Paediatric Autoimmunity and Cell Therapy (IMPACT) working group*:
Jon Burnham, Aimee Hersh, Elena Hsieh, Ryan Mitacek, Alexander Rankin, Rebecca Scobell, Melissa Tesher

Affiliations

¹ Division of Immunology, Boston Children's Hospital, Boston, MA, USA.
² Department of Paediatrics, Division of Rheumatology, Ohio State University, Columbus, OH, USA.
³ Nationwide Children's Hospital, Columbus, OH, USA.
⁴ The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Department of Paediatrics, Section of Rheumatology, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO, USA.
⁶ Juvenile Myositis Pathogenesis and Therapeutics Unit, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
⁷ Departments of Medicine and Paediatrics (Rheumatology), Duke University School of Medicine, Durham, NC, USA.
⁸ Lupus Genomics and Global Health Disparities Unit, National Institute of Arthritis Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
⁹ Center for Cancer and Immunology Research and Division of Allergy and Immunology, Children's National Hospital, Washington, DC, USA.
¹⁰ GW Cancer Center, George Washington University School of Medicine, Washington, DC, USA.
¹¹ Paediatric Translational Research Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.
¹² Departments of Internal Medicine and Paediatrics, Sections of Rheumatology and Paediatric Rheumatology, University of Chicago Medicine, Chicago, IL, USA.
¹³ Department of Medicine, Division of Rheumatology, University of Pennsylvania, Philadelphia, PA, USA.
¹⁴ Department of Paediatrics, Division of Paediatric Allergy, Immunology and Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁵ Division of Rheumatology, Hospital for Sick Children, Department of Paediatrics, Temerty Faculty of Medicine, University of Toronto, Toronto, Canada.
¹⁶ Department of Paediatrics, Division of Paediatric Oncology, University of Washington, Seattle, WA, USA.
¹⁷ Seattle Children's Therapeutics, Seattle Children's Hospital, Seattle, WA, USA.
¹⁸ Department of Paediatrics, Division of Rheumatology, University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
¹⁹ Division of Oncology, Cellular Therapy and Transplantation Section, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
²⁰ Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, AZ, USA.
²¹ Seattle Children's Research Institute, Seattle, WA, USA.
²² Department of Paediatrics, University of Washington School of Medicine, Seattle, WA, USA.
²³ Dana Farber Cancer Institute/Boston Children's Hospital Center for Cancer and Blood Disorders, Boston, MA, USA.
²⁴ Paediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
²⁵ Department of Paediatrics, Division of Paediatric Rheumatology, Duke University School of Medicine, Durham, NC, USA.
²⁶ Department of Paediatrics, Division of Hematology, Oncology, Blood and Marrow Transplant, The Ohio State University, Nationwide Children's Hospital, Columbus, OH, USA. margaret.lamb2@nationwidechildrens.org.

^# Contributed equally.

PMID: 40603629
DOI: 10.1038/s41584-025-01272-3

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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Conflict of interest statement

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.

References

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

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

Authors

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Abstract

Conflict of interest statement

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