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

  • Mark B. Geyer
  • Jae H. Park
  • Renier J. BrentjensEmail author
Chapter
Part of the Advances and Controversies in Hematopoietic Transplantation and Cell Therapy book series (ACHTCT)

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.

Keywords

Chimeric antigen receptor T-cell Leukemia Immunotherapy CD19 CD28 4-1BB 

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Mark B. Geyer
    • 1
    • 2
    • 3
    • 4
  • Jae H. Park
    • 1
    • 2
    • 3
    • 4
  • Renier J. Brentjens
    • 1
    • 2
    • 3
    • 4
    • 5
    Email author
  1. 1.Department of MedicineMemorial Sloan Kettering Cancer CenterNew YorkUSA
  2. 2.Leukemia Service and Cellular Therapeutics Center, Division of Hematologic Oncology, Department of MedicineMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  3. 3.Joan and Sanford I. Weill Department of MedicineWeill Cornell Medical CollegeNew YorkUSA
  4. 4.Center for Cell EngineeringMemorial Sloan Kettering Cancer CenterNew YorkUSA
  5. 5.Molecular Pharmacology and Chemistry ProgramMemorial Sloan Kettering Cancer CenterNew YorkUSA

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