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The quintessential role for CAR T cell therapy in children, adolescents and young adults with cancer

Nature Reviews Clinical Oncology (2026)Cite this article

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Abstract

Early successes achieved with the CD19-targeted chimeric antigen receptor (CAR) T cell product tisagenlecleucel for the treatment of paediatric B cell acute lymphoblastic leukaemia (B-ALL) led to a historic first FDA approval of a gene therapy. Widespread CAR T cell commercialization followed, along with expansion to other indications and earlier disease settings owing to clear survival benefits. However, commercial development of additional cell therapies for paediatric malignancies has stagnated, despite several products being brought to market as treatments for various haematological malignancies in adults. In contrast to the consistent efficacy achieved across B cell malignancies, CAR T cell approaches have yet to demonstrate durable activity in patients with acute myeloid leukaemia (AML), T cell acute lymphoblastic leukaemia, solid tumours and/or central nervous system cancers, with both biological factors and broader issues of development and access constraining the field. Herein, we showcase the foundational leaps achieved through the initial trials and commercialization of CAR T cell products and contextualize how these early experiences have moulded the field. We review currently approved and investigational CAR T cell therapies for paediatric and young-adult patients, including key considerations regarding safety, access and future directions. We also discuss additional immunotherapy options that guide clinical decision-making regarding optimal utilization of CAR T cells. Although clearly tolerable and efficacious, the CD19-targeted CAR T cell strategy requires ongoing refinement, and research efforts are now geared towards fully exploiting CAR T cells and other immunotherapies to improve survival with broadened access across disease states.

Key points

  • Three chimeric antigen receptor (CAR) T cell products are approved for the treatment of B cell acute lymphoblastic leukaemia (B-ALL), although only tisagenlecleucel is licensed for use in paediatric patients, and for limited indications, with a resultant reliance on this single agent for the survival gains conferred by CAR T cell therapy in paediatric B-ALL.

  • Despite high response rates in children and young adults receiving tisagenlecleucel for B-ALL, relapse rates of ~50% present an urgent need to develop and further study optimized CAR T cell constructs and approaches.

  • Risk stratification based on pre-infusion clinical characteristics can identify subsets of patients who are at high risk of CAR T cell resistance and toxicities, and thus guide optimal bridging and consolidative strategies.

  • Current CAR T cell therapy achieves excellent health-related quality of life, with low rates of treatment-related morbidity and mortality, with a tolerability profile permissive to further development of CAR T cell therapies for non-B-cell malignancies and even non-malignant diseases.

  • CAR T cells provide unique advantages over other immunotherapies, yet the optimal sequencing of these treatments, including the role of haematopoietic stem cell transplantation, remains an active area of research.

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Acknowledgements

The work of N.N.S is supported in part by the Intramural Research Program, Center of Cancer Research, National Cancer Institute and National Institutes of Health (NIH) Clinical Center (grant ZIA BC 011823). S.L.M. is a Scholar in Clinical Research of The Leukaemia & Lymphoma Society.

Author information

Authors and Affiliations

  1. Division of Pediatric Hematology/Oncology/Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford Medicine, Stanford, CA, USA

    Liora Schultz

  2. Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA

    Kevin McNerney

  3. Department of Pediatrics, University of Washington, Ben Towne Center for Childhood Cancer Research, Seattle Children’s Research Institute, Seattle, WA, USA

    Adam J. Lamble & Corinne Summers

  4. Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands

    Friso G. Calkoen & Claudia Rossig

  5. Department of Pediatric Hematology, Hôpital Universitaire Robert Debré, Assistance Publique-Hôpitaux de Paris and Université Paris Cité, Paris, France

    Andre Baruchel

  6. Pediatric Hematology-Oncology Unit, Division of Pediatrics, Department of Woman-Mother-Child, University Hospital of Lausanne and University of Lausanne, Lausanne, Switzerland

    Francesco Ceppi

  7. Department of Pediatrics, Stem Cell Transplantation and Cellular Therapies Service, Memorial Sloan Kettering, New York, NY, USA

    Kevin J. Curran

  8. Children’s Hospital Colorado and the University of Colorado School of Medicine, Aurora, CO, USA

    Lia Gore

  9. Division of Hematology, Oncology, Blood and Bone Marrow Transplant, Department of Pediatrics, Nationwide Children’s Hospital, The Ohio State University College of Medicine, Columbus, OH, USA

    Margaret Lamb

  10. Division of Oncology and Cancer Immunotherapy Program, Children’s Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Shannon L. Maude & Susan R. Rheingold

  11. Division of Hematology and Oncology, Intermountain Primary Children’s Hospital, Huntsman Cancer Institute, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, UT, USA

    Michael A. Pulsipher

  12. Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Emory University, Atlanta, GA, USA

    Muna Qayed

  13. Division of Hematology, Oncology, Stem Cell Transplantation, and Regenerative Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA

    Sneha Ramakrishna

  14. Department of Pediatric Hematology and Oncology, University Children’s Hospital Muenster, Muenster, Germany

    Claudia Rossig

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

    Sara K. Silbert & Nirali N. Shah

  16. MACC Fund Center for Cancer and Blood Disorders, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA

    Angela Steineck

  17. Department of Pediatrics and Carbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Christian M. Capitini

  18. Division of Hematology–Oncology, Cancer and Blood Disease Institute, Children’s Hospital Los Angeles, Los Angeles, CA, USA

    Deepa Bhojwani

  19. Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Deepa Bhojwani

  20. Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Rebecca A. Gardner

  21. Department of Haematology, Great Ormond Street Hospital for Children, London, UK

    Sara Ghorashian

  22. Developmental Biology and Cancer, UCL Great Ormond Street Institute of Child Health, London, UK

    Sara Ghorashian

Authors
  1. Liora Schultz
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  2. Kevin McNerney
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  3. Adam J. Lamble
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  4. Friso G. Calkoen
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  5. Andre Baruchel
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  6. Francesco Ceppi
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  7. Kevin J. Curran
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  8. Lia Gore
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  9. Margaret Lamb
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  10. Shannon L. Maude
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  11. Michael A. Pulsipher
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  12. Muna Qayed
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  13. Sneha Ramakrishna
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  14. Susan R. Rheingold
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  15. Claudia Rossig
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  16. Sara K. Silbert
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  17. Angela Steineck
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  18. Corinne Summers
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  19. Christian M. Capitini
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  20. Deepa Bhojwani
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  21. Rebecca A. Gardner
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  22. Sara Ghorashian
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  23. Nirali N. Shah
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Contributions

L.S., K.McN., A.J.L., F.G.C., A.B., F.C., K.J.C., L.G., M.L., S.L.M., M.A.P., S.R., C.S., C.M.C., D.B., R.A.G., S.G. and N.N.S. researched data for the article. L.S., K.McN., A.J.L., F.G.C., A.B., F.C., K.J.C., L.G., M.L., S.L.M., M.A.P., S.R., S.R.R., S.K.S., A.S., C.S., C.M.C., D.B., R.A.G., S.G. and N.N.S. wrote the manuscript. All authors contributed substantially to discussions of the content and reviewed and/or edited the manuscript before submission. This Review was conceptualized and led by L.S. and N.N.S.

Corresponding authors

Correspondence to Liora Schultz or Nirali N. Shah.

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Competing interests

L.G. has received travel funding and honoraria from Amgen. S.L.M. has received research support for clinical trials sponsored by Luminary Therapeutics. M.A.P. has served on advisory boards for Autolus, bluebird bio, Cargo Therapeutics, Garuda/Stratus Therapeutics, GentiBio, Mesoblast, Novartis and Pfizer; and had received research support from Adaptive Biotech and Miltenyi Biotec. M.Q. has received honoraria from Medexus. S.R.R. declares consultancy roles for Amgen and Pfizer. C.R. has received honoraria from Amgen and Novartis. C.M.C. reports honoraria from Bayer, Nektar Therapeutics and Novartis; and has equity interest in Elephas. D.B. declares research funding from Wugen. R.A.G. has patents related to CAR T cell technologies licensed with royalties paid from Juno Therapeutics. N.N.S. declares research funding from Cargo Therapeutics, Lentigen and Vor Bio; has attended advisory board meetings (no honoraria) for ImmunoACT, Sobi and Vor Bio; and receives royalties from Cargo Therapeutics. The other authors declare no competing interests.

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Nature Reviews Clinical Oncology thanks E. Jacoby, M. Maus and the other, anonymous, reviewers for their contribution to the peer review of this work.

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Schultz, L., McNerney, K., Lamble, A.J. et al. The quintessential role for CAR T cell therapy in children, adolescents and young adults with cancer. Nat Rev Clin Oncol (2026). https://doi.org/10.1038/s41571-025-01115-w

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