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双特异性抗体——弥漫性大B细胞淋巴瘤患者的新希望。

Bispecific Antibodies-A New Hope for Patients with Diffuse Large B-Cell Lymphoma.

作者信息

Mihaila Romeo Gabriel, Todor Samuel B

机构信息

Faculty of Medicine, "Lucian Blaga" University of Sibiu, 550024 Sibiu, Romania.

出版信息

J Clin Med. 2025 Aug 6;14(15):5534. doi: 10.3390/jcm14155534.


DOI:10.3390/jcm14155534
PMID:40807154
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12347617/
Abstract

T-cell-engaging antibodies are a promising new type of treatment for patients with refractory or relapsed (R/R) diffuse large B-cell lymphoma, which has changed the prognosis and evolution of these patients in clinical trials. Bispecific antibodies (BsAbs) bind to two different targets (B and T lymphocytes) at the same time and in this way mimic the action of CAR (chimeric antigen receptor) T-cells. They are the T-cell-engaging antibodies most used in practice and are a solution for patients who do not respond to second- or later-line therapies, including chemoimmunotherapy, followed by salvage chemotherapy and hematopoietic stem cell transplantation. They are a therapeutic option for patients who are ineligible for CAR T-cell therapy and are also active in those with prior exposure to CAR T-cell treatment. A remarkable advantage of BsAbs is their rapid availability, even if the disease progresses rapidly, unlike CAR T-cell treatment, and they avoid the practical and financial challenges raised by autologous CAR T-cell therapies. CAR-T has been proven to have better efficacy compared to BsAbs, but cytokine release syndrome and neurotoxicity have appeared significantly more frequently in patients treated with CAR T-cells. The possibility of combining BsAbs with chemotherapy and their administration for relapses or as a frontline therapy is being studied to increase their efficacy. BsAbs are a life-saving therapy for many patients with diffuse large B-cell malignant non-Hodgkin's lymphoma (NHL) who have a poor prognosis with classical therapies, but are not without adverse effects and require careful monitoring.

摘要

T细胞接合抗体是难治性或复发性(R/R)弥漫性大B细胞淋巴瘤患者一种很有前景的新型治疗方法,在临床试验中改变了这些患者的预后和病程。双特异性抗体(BsAbs)同时结合两个不同靶点(B淋巴细胞和T淋巴细胞),从而模拟嵌合抗原受体(CAR)T细胞的作用。它们是实际应用中最常用的T细胞接合抗体,为对二线或后续治疗(包括化疗免疫治疗)无反应的患者提供了一种解决方案,这些患者后续还需接受挽救性化疗和造血干细胞移植。对于不符合CAR T细胞治疗条件的患者,BsAbs是一种治疗选择,对于既往接受过CAR T细胞治疗的患者也有活性。BsAbs的一个显著优势是即使疾病进展迅速,它们也能快速获得,这与CAR T细胞治疗不同,而且它们避免了自体CAR T细胞疗法带来的实际和经济挑战。与BsAbs相比,CAR-T已被证明具有更好的疗效,但接受CAR T细胞治疗的患者中,细胞因子释放综合征和神经毒性的出现频率明显更高。目前正在研究将BsAbs与化疗联合使用以及将其用于复发或作为一线治疗的可能性,以提高其疗效。对于许多采用传统疗法预后较差的弥漫性大B细胞恶性非霍奇金淋巴瘤(NHL)患者来说,BsAbs是一种挽救生命的疗法,但并非没有不良反应,需要仔细监测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1303/12347617/9cee315e310f/jcm-14-05534-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1303/12347617/047aa473d88e/jcm-14-05534-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1303/12347617/130fad185a51/jcm-14-05534-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1303/12347617/9cee315e310f/jcm-14-05534-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1303/12347617/047aa473d88e/jcm-14-05534-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1303/12347617/130fad185a51/jcm-14-05534-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1303/12347617/9cee315e310f/jcm-14-05534-g003.jpg

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本文引用的文献

[1]
New bispecific antibodies in diffuse large B-cell lymphoma.

Haematologica. 2025-7-1

[2]
Mosunetuzumab plus Pola-CHP compared with Pola-R-CHP in previously untreated DLBCL: final results from a phase 2 study.

Blood Adv. 2025-5-27

[3]
Epcoritamab plus GemOx in transplant-ineligible relapsed/refractory DLBCL: results from the EPCORE NHL-2 trial.

Blood. 2025-4-10

[4]
Odronextamab monotherapy in R/R DLBCL after progression with CAR T-cell therapy: primary analysis of the ELM-1 study.

Blood. 2025-4-3

[5]
Dexamethasone is associated with reduced frequency and intensity of cytokine release syndrome compared with alternative corticosteroid regimens as premedication for glofitamab in patients with relapsed/refractory large B-cell lymphoma.

Haematologica. 2025-4-1

[6]
Impact of prior CAR T-cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory B-cell lymphomas.

Blood Adv. 2025-2-25

[7]
Glofitamab plus gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx for relapsed or refractory diffuse large B-cell lymphoma (STARGLO): a global phase 3, randomised, open-label trial.

Lancet. 2024-11-16

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Leukemia. 2024-12

[9]
Blinatumomab after R-CHOP bridging therapy for patients with Richter transformation: a phase 2 multicentre trial.

Nat Commun. 2024-8-9

[10]
The Evolving Role of Bispecific Antibodies in Diffuse Large B-Cell Lymphoma.

J Pers Med. 2024-6-21

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