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T-Cell Receptor-Engineered Cells for the Treatment of Hematologic Malignancies

  • CART and Immunotherapy (M Ruella, Section Editor)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Recent attention in adoptive immunotherapy for hematologic malignancies has focused on lymphocytes expressing chimeric antigen receptors. An alternative technique to redirect the immune system toward cancer cells involves the use of T-cells carrying an engineered tumor-recognizing T-cell receptor (TCR). This approach allows targeting of surface or intracellular/nuclear proteins as long as they are processed and presented on the cell surface by human leukocyte antigen molecules. Several trials in advanced solid tumors, particularly melanoma and synovial sarcoma, support the validity of this strategy, although tumor responses have often been short-lived. Emerging data from patients with multiple myeloma and myeloid neoplasms suggest that the benefit of TCR-modified cells may extend to blood cancers. Methodological refinements may be necessary to increase the in vivo persistence and functionality of these cells. Particularly with affinity-enhanced TCRs, however, more effective therapies may increase the potential for serious toxicity due to the unexpected on- or off-target reactivity.

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Acknowledgments

Roland B. Walter is a Leukemia & Lymphoma Society Scholar in Clinical Research.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA

    Nasheed M. Hossain

  2. Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, D2-190, Seattle, WA, 98109-1024, USA

    Aude G. Chapuis & Roland B. Walter

  3. Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, WA, USA

    Aude G. Chapuis

  4. Department of Medicine, Division of Hematology, University of Washington, Seattle, WA, USA

    Roland B. Walter

  5. Department of Epidemiology, University of Washington, Seattle, WA, USA

    Roland B. Walter

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  1. Nasheed M. Hossain
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  2. Aude G. Chapuis
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Correspondence to Roland B. Walter.

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Conflict of Interest

Nasheed M. Hossain and Aude G. Chapuis declare no potential conflicts of interest.

Roland B. Walter has received research funding from Amgen, Inc., Amphivena Therapeutics, Inc., Covagen AG, and Seattle Genetics, Inc., and is a consultant for Amphivena Therapeutics, Inc., Covagen AG, Emergent Biosolutions, Inc., Janssen Pharmaceuticals, Inc., and Pfizer, Inc.

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This article does not contain any otherwise unpublished studies with human subjects or animals that were performed by the authors.

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This article is part of the Topical Collection on CART and Immunotherapy

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Hossain, N.M., Chapuis, A.G. & Walter, R.B. T-Cell Receptor-Engineered Cells for the Treatment of Hematologic Malignancies. Curr Hematol Malig Rep 11, 311–317 (2016). https://doi.org/10.1007/s11899-016-0327-0

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