CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Bispecific Antibodies-A New Hope for Patients with Diffuse Large B-Cell Lymphoma.
Bispecific Antibodies-A New Hope for Patients with Diffuse Large B-Cell Lymphoma.
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T 细胞衔接抗体是治疗难治或复发(R/R)弥漫大 B 细胞淋巴瘤的一类有前景的新疗法,临床试验显示其改变了患者的预后和疾病进程。双特异性抗体(BsAb)可同时结合两种不同靶点(B、T 淋巴细胞),从而模拟 CAR-T 细胞的作用。它们是目前实践中应用最广泛的 T 细胞衔接抗体,可用于二线及后续治疗(包括化学免疫治疗)无应答,且随后挽救化疗和造血干细胞移植也未奏效的患者。BsAb 是不适合接受 CAR-T 治疗患者的一种治疗选择,对既往接受过 CAR-T 的患者也有活性。BsAb 的显著优势是可快速获得,即使疾病进展迅速亦可使用;与 CAR-T 治疗不同,它们避免了自体 CAR-T 疗法在实际操作和经济方面的挑战。已有证据表明 CAR-T 的疗效优于 BsAb,但接受 CAR-T 的患者 CRS 和神经毒性的发生率显著更高。目前正在研究将 BsAb 与化疗联合,以及用于复发时或一线治疗,以提高疗效。对于经典疗法预后不良的许多弥漫大 B 细胞恶性非霍奇金淋巴瘤(NHL)患者,BsAb 是挽救生命的治疗,但仍有不良反应,需要仔细监测。
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.
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