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CD20 双特异性抗体在淋巴瘤的体外和 CLL 的体内模型中提高了对 CD19-CAR T 细胞的反应。

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

机构信息

Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany.

Molecular Medicine Partnership Unit, Heidelberg, Germany.

出版信息

Blood. 2024 Aug 15;144(7):784-789. doi: 10.1182/blood.2023022682.


DOI:10.1182/blood.2023022682
PMID:38805637
Abstract

Relapse after anti-CD19 chimeric antigen receptor (CD19-CAR) occurs in a substantial proportion of patients with lymphoid malignancies. We assessed the potential benefits of co-administering CD20-targeting bispecific antibodies (CD20-BsAbs) with CD19-CAR T cells with the aim of enhancing immunotherapeutic efficacy. Addition of CD20-BsAbs to cocultures of CD19-CARs and primary samples of B-cell malignancies, comprising malignant B cells and endogenous T cells, significantly improved killing of malignant cells and enhanced the expansion of both endogenous T cells and CD19-CAR T cells. In an immunocompetent mouse model of chronic lymphocytic leukemia, relapse after initial treatment response frequently occurred after CD19-CAR T-cell monotherapy. Additional treatment with CD20-BsAbs significantly enhanced the treatment response and led to improved eradication of malignant cells. Higher efficacy was accompanied by improved T-cell expansion with CD20-BsAb administration and led to longer survival with 80% of the mice being cured with no detectable malignant cell population within 8 weeks of therapy initiation. Collectively, our in vitro and in vivo data demonstrate enhanced therapeutic efficacy of CD19-CAR T cells when combined with CD20-BsAbs in B-cell malignancies. Activation and proliferation of both infused CAR T cells and endogenous T cells may contribute to improved disease control.

摘要

抗 CD19 嵌合抗原受体 (CD19-CAR) 治疗后,相当一部分淋巴恶性肿瘤患者会出现疾病复发。我们评估了共给予 CD20 靶向双特异性抗体 (CD20-BsAb) 与 CD19-CAR T 细胞的潜在益处,旨在增强免疫治疗效果。将 CD20-BsAb 添加到 CD19-CAR 和 B 细胞恶性肿瘤的原代样本的共培养物中,显著改善了对恶性细胞的杀伤作用,并增强了内源性 T 细胞和 CD19-CAR T 细胞的扩增。在慢性淋巴细胞白血病的免疫功能正常的小鼠模型中,在初始治疗反应后,CD19-CAR T 细胞单药治疗后经常发生疾病复发。用 CD20-BsAb 进行额外治疗显著增强了治疗反应,并导致恶性细胞的清除得到改善。疗效提高伴随着 CD20-BsAb 给药时 T 细胞的扩增改善,并且在 8 周的治疗开始后,80%的小鼠被治愈,未检测到恶性细胞群,从而延长了生存时间。总之,我们的体外和体内数据表明,在 B 细胞恶性肿瘤中,CD19-CAR T 细胞与 CD20-BsAb 联合使用具有增强的治疗效果。输注的 CAR T 细胞和内源性 T 细胞的激活和增殖可能有助于改善疾病控制。

相似文献

[1]
CD20-bispecific antibodies improve response to CD19-CAR T cells in lymphoma in vitro and CLL in vivo models.

Blood. 2024-8-15

[2]
CD20-CD19 Bispecific CAR T Cells for the Treatment of B-Cell Malignancies.

Hum Gene Ther. 2017-12

[3]
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

[4]
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

[5]
Loop CD20/CD19 CAR-T cells eradicate B-cell malignancies efficiently.

Sci China Life Sci. 2023-4

[6]
T Cells Expressing CD19/CD20 Bispecific Chimeric Antigen Receptors Prevent Antigen Escape by Malignant B Cells.

Cancer Immunol Res. 2016-4-8

[7]
Development of a compact bidirectional promoter-driven dual chimeric antigen receptor (CAR) construct targeting CD19 and CD20 in the Sleeping Beauty (SB) transposon system.

J Immunother Cancer. 2024-4-27

[8]
Interaction kinetics with transcriptomic and secretory responses of CD19-CAR natural killer-cell therapy in CD20 resistant non-hodgkin lymphoma.

Leukemia. 2019-11-26

[9]
Optimized tandem CD19/CD20 CAR-engineered T cells in refractory/relapsed B-cell lymphoma.

Blood. 2020-10-1

[10]
Transforming CLL management with immunotherapy: Investigating the potential of CAR T-cells and bispecific antibodies.

Semin Hematol. 2024-4

引用本文的文献

[1]
Bystander CARCD8 T cells in a CAR-T cell product can expand and enhance the antitumor effects of a bispecific antibody.

J Immunother Cancer. 2025-6-24

[2]
A question of TiME: how microenvironmental interactions shape response to immunotherapy in CLL and Richter Transformation.

Front Immunol. 2025-5-29

[3]
How we treat mantle cell lymphoma with cellular therapy in 2025: the European and American perspectives.

Bone Marrow Transplant. 2025-4-14

[4]
Updates on Chimeric Antigen Receptor T-Cells in Large B-Cell Lymphoma.

Biomedicines. 2024-12-11

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