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Clinical development of anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma.

作者信息

Makita Shinichi, Yoshimura Kiyoshi, Tobinai Kensei

机构信息

Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.

Department of Experimental Therapeutics and Exploratory Oncology Research and Clinical Trial Center, National Cancer Center Hospital, Tokyo, Japan.

出版信息

Cancer Sci. 2017 Jun;108(6):1109-1118. doi: 10.1111/cas.13239. Epub 2017 May 25.


DOI:10.1111/cas.13239
PMID:28301076
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5480083/
Abstract

B-cell non-Hodgkin lymphoma (B-NHL) is the most frequent hematological malignancy. Although refined chemotherapy regimens and several new therapeutics including rituximab, a chimeric anti-CD20 monoclonal antibody, have improved its prognosis in recent decades, there are still a substantial number of patients with chemorefractory B-NHL. Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is expected to be an effective adoptive cell treatment and has the potential to overcome the chemorefractoriness of B-cell leukemia and lymphoma. Recently, several clinical trials have shown remarkable efficacy of anti-CD19 CAR T-cell therapy, not only in B-acute lymphoblastic leukemia but also in B-NHL. Nonetheless, there are several challenges to overcome before introduction into clinical practice, such as: (i) further refinement of the manufacturing process, (ii) further improvement of efficacy, (iii) finding the optimal infusion cell dose, (iv) optimization of lymphocyte-depleting chemotherapy, (v) identification of the best CAR structure, and (vi) optimization of toxicity management including cytokine release syndrome, neurologic toxicity, and on-target off-tumor toxicity. Several ways to solve these problems are currently under study. In this review, we describe the updated clinical data regarding anti-CD19 CAR T-cell therapy, with a focus on B-NHL, and discuss the clinical implications and perspectives of CAR T-cell therapy.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3631/5480083/d28264b5608c/CAS-108-1109-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3631/5480083/126957b557af/CAS-108-1109-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3631/5480083/3d49364c3807/CAS-108-1109-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3631/5480083/29f45d9b45e1/CAS-108-1109-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3631/5480083/d28264b5608c/CAS-108-1109-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3631/5480083/126957b557af/CAS-108-1109-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3631/5480083/3d49364c3807/CAS-108-1109-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3631/5480083/29f45d9b45e1/CAS-108-1109-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3631/5480083/d28264b5608c/CAS-108-1109-g004.jpg

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Clinical development of anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma.

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本文引用的文献

[1]
Phase 1 Results of ZUMA-1: A Multicenter Study of KTE-C19 Anti-CD19 CAR T Cell Therapy in Refractory Aggressive Lymphoma.

Mol Ther. 2017-1-4

[2]
Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells.

Sci Transl Med. 2017-1-25

[3]
A Rapid Cell Expansion Process for Production of Engineered Autologous CAR-T Cell Therapies.

Hum Gene Ther Methods. 2016-12

[4]
Kinase inhibitor ibrutinib to prevent cytokine-release syndrome after anti-CD19 chimeric antigen receptor T cells for B-cell neoplasms.

Leukemia. 2017-1

[5]
Toxicity and management in CAR T-cell therapy.

Mol Ther Oncolytics. 2016-4-20

[6]
Immunotherapy of non-Hodgkin's lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified T cells.

Sci Transl Med. 2016-9-7

[7]
Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies.

J Clin Invest. 2016-10-3

[8]
Chimeric antigen receptor T cells targeting Fc μ receptor selectively eliminate CLL cells while sparing healthy B cells.

Blood. 2016-8-17

[9]
Armored CAR T-cells: utilizing cytokines and pro-inflammatory ligands to enhance CAR T-cell anti-tumour efficacy.

Biochem Soc Trans. 2016-4-15

[10]
T Cells Expressing CD19/CD20 Bispecific Chimeric Antigen Receptors Prevent Antigen Escape by Malignant B Cells.

Cancer Immunol Res. 2016-4-8

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