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靶向 CD20 的肿瘤免疫治疗进展:从开创性单克隆抗体到嵌合抗原受体修饰 T 细胞

英文原题:Advancements in cancer immunotherapies targeting CD20: from pioneering monoclonal antibodies to chimeric antigen receptor-modified T cells.

查看英文原题

Advancements in cancer immunotherapies targeting CD20: from pioneering monoclonal antibodies to chimeric antigen receptor-modified T cells.

PubMed 2024/04/04(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

CD20主要位于B细胞表面,在其发育、分化和活化过程中发挥关键作用,是治疗B细胞恶性肿瘤的重要靶点。以利妥昔单抗为代表的抗CD20单克隆抗体取得突破,革新了B细胞恶性肿瘤的预后。利妥昔单抗获批用于多种血液系统恶性肿瘤,标志着癌症治疗模式转变。目前,靶向CD20的免疫疗法仍在快速发展。除传统单克隆抗体外,相关进展还包括抗体药物偶联物(ADC)、双特异性抗体(BsAb)和嵌合抗原受体(CAR)修饰T细胞。ADC结合抗体的精准靶向和药物的细胞毒作用,有望提高治疗效能。尤其是CD20×CD3构建体等BsAb可将细胞毒性T细胞重定向至癌细胞,提升治疗精准度和效力。CAR-T 细胞是治疗血液系统恶性肿瘤的有前景策略,也是个体化治疗的典型形式。目前,多种新疗法正在临床试验中评估。本文全面总结靶向CD20的疗法,强调其进展和持续存在的挑战。尽管取得重大进展,相关不良事件和耐药仍是关键问题。理解并缓解这些挑战,是确保靶向CD20免疫疗法持续成功的关键。

展开英文摘要原文

CD20 located predominantly on the B cells plays a crucial role in their development, differentiation, and activation, and serves as a key therapeutic target for the treatment of B-cell malignancies. The breakthrough of monoclonal antibodies directed against CD20, notably exemplified by rituximab, revolutionized the prognosis of B-cell malignancies. Rituximab, approved across various hematological malignancies, marked a paradigm shift in cancer treatment. In the current landscape, immunotherapies targeting CD20 continue to evolve rapidly. Beyond traditional mAbs, advancements include antibody-drug conjugates (ADCs), bispecific antibodies (BsAbs), and chimeric antigen receptor-modified (CAR) T cells. ADCs combine the precision of antibodies with the cytotoxic potential of drugs, presenting a promising avenue for enhanced therapeutic efficacy.

BsAbs, particularly CD20xCD3 constructs, redirect cytotoxic T cells to eliminate cancer cells, thereby enhancing both precision and potency in their therapeutic action. CAR-T cells stand as a promising strategy for combatting hematological malignancies, representing one of the truly personalized therapeutic interventions. Many new therapies are currently being evaluated in clinical trials.

This review serves as a comprehensive summary of CD20-targeted therapies, highlighting the progress and challenges that persist. Despite significant advancements, adverse events associated with these therapies and the development of resistance remain critical issues. Understanding and mitigating these challenges is paramount for the continued success of CD20-targeted immunotherapies.

论文信息

作者
Dabkowska A、Domka K、Firczuk M
单位
Laboratory of Immunology, Mossakowski Medical Research Institute Polish Academy of Sciences, Warsaw, Poland.Poland
文献类型
综述 · 非美国政府资助研究
期刊
Frontiers in immunology2024
原文标识
PubMed 38638442 · DOI 10.3389/fimmu.2024.1363102