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Mechanisms of Resistance and Relapse After CAR-T Cell Therapy

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Gene and Cellular Immunotherapy for Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Chimeric antigen receptor (CAR)-engineered T cells can mediate impressive responses in a subset of patients with B cell malignancies. Clinical trial and real-world data, however, reveal that most patients will not achieve durable remission. Therapeutic failure appears to segregate into two distinct models: inherent resistance, in which there is no meaningful disease response after treatment, or acquired resistance, in which disease recurrence follows a transient response. A host of studies have identified that both forms of failure can result from tumor-intrinsic evasion mechanisms which can be antigen-dependent or independent. Alternatively, resistance or relapse can occur due to T cell dysfunction, both intrinsic to the cells prior to infusion or that develops after delivery to patients. In this chapter, we review the mechanistic and correlative studies investigating resistance to CAR-T cells, and discuss strategies designed to overcome this significant hurdle to the broader success of this therapy.

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Author information

Authors and Affiliations

  1. Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA

    Mehmet Emrah Selli & Nathan Singh

  2. Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    Prarthana Dalal

  3. Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Sattva S. Neelapu

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  1. Mehmet Emrah Selli
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  2. Prarthana Dalal
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  3. Sattva S. Neelapu
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  4. Nathan Singh
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Correspondence to Nathan Singh .

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Editors and Affiliations

  1. Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA

    Armin Ghobadi

  2. Department of Medicine Pathology & Immunology, Division of Oncology, Washington University School of Medicine, Saint Louis, MO, USA

    John F. DiPersio

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Selli, M.E., Dalal, P., Neelapu, S.S., Singh, N. (2022). Mechanisms of Resistance and Relapse After CAR-T Cell Therapy. In: Ghobadi, A., DiPersio, J.F. (eds) Gene and Cellular Immunotherapy for Cancer . Cancer Drug Discovery and Development. Humana, Cham. https://doi.org/10.1007/978-3-030-87849-8_12

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  • DOI: https://doi.org/10.1007/978-3-030-87849-8_12

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  • Publisher Name: Humana, Cham

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