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

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Cell and Gene Therapies

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Abstract

Within the past several years, renewed interest in immunotherapy has been observed in multiple fields of oncology, including antibody-based therapeutics (e.g., checkpoint blockade) and adoptive cellular therapies. In the field of adult leukemias, such interest has been driven by the limitations of presently available therapies to induce durable remissions reliably in patients with relapsed and refractory leukemia. The adoptive transfer of genetically modified autologous T-cells aims to rapidly establish specific antitumor activity. This strategy requires targeting of autologous T-cells by means of a transgene-encoded antigen receptor, consisting of a chimeric antigen receptor (CAR), as will be discussed herein, or T-cell receptor (TCR) chains. CD19 is nearly universally expressed by B-ALL, CLL, and hairy cell leukemia, while not expressed on normal tissues other than B-cells, including multipotent hematopoietic progenitor cells. Multiple generations of CARs have been developed and investigated in clinical studies and will be discussed in this review. In this chapter, we review clinical outcomes of adults with leukemia treated with CAR T-cells, toxicities associated with CAR T-cell administration, present challenges limiting therapeutic efficacy, and future directions, including novel targets and enhancements to improve antileukemic activity.

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Author information

Authors and Affiliations

  1. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Mark B. Geyer, Jae H. Park & Renier J. Brentjens

  2. Leukemia Service and Cellular Therapeutics Center, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Mark B. Geyer, Jae H. Park & Renier J. Brentjens

  3. Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, New York, NY, USA

    Mark B. Geyer, Jae H. Park & Renier J. Brentjens

  4. Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Mark B. Geyer, Jae H. Park & Renier J. Brentjens

  5. Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Renier J. Brentjens

Authors
  1. Mark B. Geyer
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  2. Jae H. Park
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  3. Renier J. Brentjens
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Corresponding author

Correspondence to Renier J. Brentjens .

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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Geyer, M.B., Park, J.H., Brentjens, R.J. (2019). Chimeric Antigen Receptor-T Cells for Leukemias in Adults: 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_5

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  • DOI: https://doi.org/10.1007/978-3-319-54368-0_5

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