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CD20-CD19 双特异性 CAR T 细胞治疗 B 细胞恶性肿瘤。

CD20-CD19 Bispecific CAR T Cells for the Treatment of B-Cell Malignancies.

机构信息

1 Center for Molecular Medicine Cologne (CMMC), University of Cologne, and Deparment I for Internal Medicine, University Hospital Cologne , Cologne, Germany.

2 Department of Pediatric Hematology and Oncology, University Children's Hospital, Eberhard Karls University , Tübingen, Germany.

出版信息

Hum Gene Ther. 2017 Dec;28(12):1147-1157. doi: 10.1089/hum.2017.126.


DOI:10.1089/hum.2017.126
PMID:29207878
Abstract

The treatment of leukemia/lymphoma by chimeric antigen receptor (CAR) redirected T cells with specificity for CD19 induced complete remissions in the majority of patients, with a realistic hope for cure. However, recent follow-up data revealed a substantial risk of relapse through leukemic cells that lack the CAR targeted antigen. In this situation, a bispecific CAR with binding domains for CD19 and CD20 is aimed at recognizing leukemic cells with only one cognate antigen. The anti-CD20-CD19 bispecific CAR induced a full T-cell response upon engagement of CD19 or CD20 on target cells showing a true "OR" gate recognition in redirecting T-cell activation. T cells with the anti-CD20-CD19 CAR efficiently killed patients' chronic lymphocytic leukemia cells in vitro. The bispecific CAR T cells cleared pediatric acute lymphocytic leukemia with a mixed CD19CD20/CD20 phenotype from the blood and bone marrow of transplanted mice, while anti-CD20 CAR T cells left CD20 leukemic cells behind without curing the disease. Data indicate the superior anti-leukemic activity in the control of leukemia, implying that the anti-CD20-CD19 bispecific CAR T cells may reduce the risk of relapse through antigen-loss leukemic cells in the long term.

摘要

嵌合抗原受体 (CAR) 修饰的 T 细胞对 CD19 的特异性治疗白血病/淋巴瘤,使大多数患者获得完全缓解,有治愈的现实希望。然而,最近的随访数据显示,通过缺乏 CAR 靶向抗原的白血病细胞存在实质性的复发风险。在这种情况下,一种具有结合 CD19 和 CD20 结合域的双特异性 CAR 旨在识别仅具有一个同源抗原的白血病细胞。抗 CD20-CD19 双特异性 CAR 在与靶细胞上的 CD19 或 CD20 结合时诱导完全 T 细胞反应,在重新定向 T 细胞激活方面表现出真正的“或”门识别。具有抗 CD20-CD19 CAR 的 T 细胞在体外有效杀伤患者慢性淋巴细胞白血病细胞。双特异性 CAR T 细胞清除了移植小鼠血液和骨髓中具有混合 CD19CD20/CD20 表型的小儿急性淋巴细胞白血病,而抗 CD20 CAR T 细胞在不治愈疾病的情况下留下了 CD20 白血病细胞。数据表明在控制白血病方面具有更好的抗白血病活性,这意味着抗 CD20-CD19 双特异性 CAR T 细胞可能会降低长期内通过抗原丢失白血病细胞复发的风险。

相似文献

[1]
CD20-CD19 Bispecific CAR T Cells for the Treatment of B-Cell Malignancies.

Hum Gene Ther. 2017-12

[2]
T Cells Expressing CD19/CD20 Bispecific Chimeric Antigen Receptors Prevent Antigen Escape by Malignant B Cells.

Cancer Immunol Res. 2016-4-8

[3]
Bispecific anti-CD20, anti-CD19 CAR T cells for relapsed B cell malignancies: a phase 1 dose escalation and expansion trial.

Nat Med. 2020-10-5

[4]
A tandem CD19/CD20 CAR lentiviral vector drives on-target and off-target antigen modulation in leukemia cell lines.

J Immunother Cancer. 2017-5-16

[5]
CD20-bispecific antibodies improve response to CD19-CAR T cells in lymphoma in vitro and CLL in vivo models.

Blood. 2024-8-15

[6]
A Syngeneic Mouse B-Cell Lymphoma Model for Pre-Clinical Evaluation of CD19 CAR T Cells.

J Vis Exp. 2018-10-16

[7]
Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor.

J Clin Oncol. 2015-2-20

[8]
Loop CD20/CD19 CAR-T cells eradicate B-cell malignancies efficiently.

Sci China Life Sci. 2023-4

[9]
Construction of a new anti-CD19 chimeric antigen receptor and the anti-leukemia function study of the transduced T cells.

Oncotarget. 2016-3-1

[10]
An analytical biomarker for treatment of patients with recurrent B-ALL after remission induced by infusion of anti-CD19 chimeric antigen receptor T (CAR-T) cells.

Sci China Life Sci. 2016-3-24

引用本文的文献

[1]
Utilizing genomics to identify novel immunotherapeutic targets in multiple myeloma high-risk subgroups.

Genome Med. 2025-7-15

[2]
Efficacy and safety of CD19 combined with CD22 or CD20 chimeric antigen receptor T-cell therapy for hematological malignancies.

Front Immunol. 2025-5-13

[3]
CD19 -targeted CAR T therapy treating hematologic malignancies: hidden danger is the next neighbor to security?

Front Immunol. 2025-3-4

[4]
Tandem CAR-T cell therapy: recent advances and current challenges.

Front Immunol. 2025-2-28

[5]
Advances in the understanding and therapeutic manipulation of cancer immune responsiveness: a Society for Immunotherapy of Cancer (SITC) review.

J Immunother Cancer. 2025-1-16

[6]
CAR-T Cells in Acute Myeloid Leukemia: Where Do We Stand?

Biomedicines. 2024-5-28

[7]
CD19/CD20 dual-targeted chimeric antigen receptor-engineered natural killer cells exhibit improved cytotoxicity against acute lymphoblastic leukemia.

J Transl Med. 2024-3-13

[8]
Advanced strategies in improving the immunotherapeutic effect of CAR-T cell therapy.

Mol Oncol. 2024-8

[9]
Targeting solid tumor antigens with chimeric receptors: cancer biology meets synthetic immunology.

Trends Cancer. 2024-4

[10]
CAR-T cell therapy: a game-changer in cancer treatment and beyond.

Clin Transl Oncol. 2024-6

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