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The SUMO Pathway in Hematomalignancies and Their Response to Therapies
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Resistance Mechanisms to CAR T-Cell Therapy and Overcoming Strategy in B-Cell Hematologic Malignancies

1
Department of Hemato-Oncology, Hanyang University Hanmaeum Changwon Hospital, Changwon 51497, Korea
2
Division of Hematology-Oncology, Department of Internal Medicine, Hanyang University College of Medicine, Hanyang University Seoul Hospital, Seoul 04763, Korea
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(20), 5010; https://doi.org/10.3390/ijms20205010
Received: 24 August 2019 / Revised: 3 October 2019 / Accepted: 9 October 2019 / Published: 10 October 2019
(This article belongs to the Special Issue Drug Resistance in Hematologic Malignancies)
Chimeric antigen receptor (CAR) T-cell therapy has shown promising clinical impact against hematologic malignancies. CD19 is a marker on the surface of normal B cells as well as most B-cell malignancies, and thus has a role as an effective target for CAR T-cell therapy. In numerous clinical data, successes with cell therapy have provided anticancer therapy as a potential therapeutic option for patients who are resistant to standard chemotherapies. However, recent growing evidence showed the limitations of the treatment such as antigen-positive relapse due to poor CAR T-cell persistence and antigen-negative relapses associated with CAR-driven mutations, alternative splicing, epitope masking, low antigen density, and lineage switching. The understanding of the resistance mechanisms to the cell therapy has developed novel potential treatment strategies, including dual-targeting therapy (dual and tandem CAR), and armored and universal CAR T-cell therapies. In this review, we provide an overview of resistance mechanisms to CD19 CAR T-cell therapy in B-cell malignancies and also review therapeutic strategies to overcome these resistances. View Full-Text
Keywords: CAR T-cell; drug resistance; B cell hematologic malignancies CAR T-cell; drug resistance; B cell hematologic malignancies
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Song, M.-K.; Park, B.-B.; Uhm, J.-E. Resistance Mechanisms to CAR T-Cell Therapy and Overcoming Strategy in B-Cell Hematologic Malignancies. Int. J. Mol. Sci. 2019, 20, 5010.

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