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Advances in Engineered T Cells

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Front. Oncol. | doi: 10.3389/fonc.2019.00126

Chimeric Antigen Receptors for T-cell Malignancies

 Lauren D. Scherer1, 2, 3*, Malcolm K. Brenner1, 2, 3 and  Maksim Mamonkin1, 2, 3*
  • 1Baylor College of Medicine, United States
  • 2Texas Children's Hospital, United States
  • 3Center for Cell and Gene Therapy, Baylor College of Medicine, United States

Development of chimeric antigen receptor (CAR)-modified T cells for the treatment of T-lineage leukemia and lymphoma has encountered several unique challenges. The most widely expressed tumor antigen targets for malignant T cells are often also expressed on non-malignant T cells. Transducing T cells with CARs targeted to these shared antigens can therefore promote over-activation or fratricide of CAR T cells, reducing their therapeutic potency. If fratricide is resolved, clinical CAR T cell activity may eliminate normal T-cell subsets and cause temporary immunosuppression. In this review, we summarize the preclinical development of CAR-based therapies for T-cell malignancies and discuss strategies to minimize toxicities associated with on-target fratricide and off-tumor activity.

Keywords: chimeric antigen receptor (CAR), Acute Lymphoblastic Leukemia, T-cell lymphoblastic leukemia or lymphoma, Non-Hodgkin lymphoma (NHL), adoptive cell therapy

Received: 11 Dec 2018; Accepted: 12 Feb 2019.

Edited by:

Rimas J. Orentas, Seattle Children's Research Institute, United States

Reviewed by:

Dina Schneider, Lentigen Technology (United States), United States
Marco Ruella, University of Pennsylvania, United States
PEIHUA LU, Lu Daopei Hospital, China  

Copyright: © 2019 Scherer, Brenner and Mamonkin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Lauren D. Scherer, Baylor College of Medicine, Houston, 77030, Texas, United States, Lauren.scherer@bcm.edu
Dr. Maksim Mamonkin, Baylor College of Medicine, Houston, 77030, Texas, United States, mamonkin@bcm.edu