In vitro comparison of CD20xCD3 biosimilar antibodies against diffuse large B-cell lymphoma (DLBCL) cell lines with different levels of expression of CD20.

IF 5.1 2区 医学 Q1 HEMATOLOGY
Joshua S Bray, Gethin R Thomas, Victoria M Smith, Adam Wright, Sandrine Jayne, Martin J S Dyer, Harriet S Walter
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引用次数: 0

Abstract

Although CD20xCD3 bispecific antibodies (BsAbs) have demonstrated transformational activity in diffuse large B-cell lymphoma (DLBCL), some patients fail to respond and others relapse. To begin to explore possible limitations, we compared the in vitro activity of four CD20xCD3 biosimilar BsAbs against four DLBCL cell lines with CD20 expression ranging over a 100-fold. All four biosimilar BsAbs demonstrated superior in vitro activity to rituximab, with biosimilar glofitamab consistently being the most potent. Moreover, biosimilar glofitamab and odronextamab retained significant activity in the presence of low-level CD20 expression. Finally, one DLBCL cell line exhibited intrinsic resistance to all four CD20xCD3 BsAbs despite inducing marked T-cell and NK-cell activation.

针对具有不同 CD20 表达水平的弥漫大 B 细胞淋巴瘤 (DLBCL) 细胞系的 CD20xCD3 生物类似抗体的体外比较。
尽管 CD20xCD3 双特异性抗体(BsAbs)在弥漫性大 B 细胞淋巴瘤(DLBCL)中显示出了变革性的活性,但一些患者没有反应,另一些患者则复发了。为了开始探索可能存在的局限性,我们比较了四种 CD20xCD3 生物类似物 BsAbs 对 CD20 表达量超过 100 倍的四种 DLBCL 细胞系的体外活性。所有四种生物类似物都显示出优于利妥昔单抗的体外活性,其中生物类似物格洛菲他单抗一直是最有效的。此外,生物类似物格洛菲他单抗和奥德龙单抗在低水平CD20表达的情况下仍具有显著的活性。最后,一种DLBCL细胞系尽管能诱导明显的T细胞和NK细胞活化,但却对所有四种CD20xCD3 BsAbs表现出内在抗性。
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来源期刊
CiteScore
8.60
自引率
4.60%
发文量
565
审稿时长
1 months
期刊介绍: The British Journal of Haematology publishes original research papers in clinical, laboratory and experimental haematology. The Journal also features annotations, reviews, short reports, images in haematology and Letters to the Editor.
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