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Chimeric Antigen Receptor T Cells for Leukemias in Children: Methods, Data, and Challenges

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Cell and Gene Therapies

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Abstract

The past few decades have brought enormous improvements in the cure rates of childhood acute leukemia; about 85% of all children with newly diagnosed acute lymphoblastic leukemia (ALL) and 50–60% with acute myeloid leukemia (AML) experience long-term disease control after multimodal treatments that often include intensified chemotherapy. Relapsed leukemia patients pose a challenging subset of the pediatric leukemic population due to highly resistant disease and, very often, underlying organ dysfunction, calling for development of novel therapeutic approaches and innovative strategies with the power to kill refractory leukemic cells. Advanced laboratory technologies have provided fresh insights into mechanisms of relapse and leukemic cell evolution. Newer formulations of older drugs, antibody-based therapies, and molecularly targeted agents are some of the current strategies under investigation for treatment of relapsed ALL. Whole-genome sequencing has allowed characterization of the transcriptional profile of the leukemic cell, facilitating targeted therapy and leading us one step closer to precision medicine. In this rapidly evolving “race” for better and nontoxic treatments, we find ourselves in an era of the new “CARs”—chimeric antigen receptor(s)—that are defining a role for immunotherapy in childhood cancers of which one was recently approved by US Food and Drug Administration for the treatment of patients up to age 25 years with B-cell precursor acute lymphoblastic leukemia (ALL) who are refractory or in second or later relapse.

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Authors and Affiliations

  1. Division of Oncology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Mala K. Talekar & Stephan A. Grupp

  2. Oncology Clinical Development, GlaxoSmithKline, Collegeville, PA, USA

    Mala K. Talekar

  3. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Stephan A. Grupp

Authors
  1. Mala K. Talekar
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  2. Stephan A. Grupp
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Correspondence to Mala K. Talekar .

Editor information

Editors and Affiliations

  1. Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Miguel-Angel Perales

  2. Cancer Treatment Centers of America, Deerfield, IL, USA

    Syed A. Abutalib

  3. Center for Cancer and Immunology Research Children’s National and The George Washington University, Division Allergy and Immunology, Washington, DC, USA

    Catherine Bollard

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Talekar, M.K., Grupp, S.A. (2019). Chimeric Antigen Receptor T Cells for Leukemias in Children: Methods, Data, and Challenges. In: Perales, MA., Abutalib, S., Bollard, C. (eds) Cell and Gene Therapies. Advances and Controversies in Hematopoietic Transplantation and Cell Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-54368-0_4

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  • DOI: https://doi.org/10.1007/978-3-319-54368-0_4

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