针对不同CD20表达水平的弥漫性大B细胞淋巴瘤（DLBCL）细胞系的CD20xCD3双特异性抗体的体外比较

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

作者信息

Bray Joshua S, Thomas Gethin R, Smith Victoria M, Wright Adam, Jayne Sandrine, Dyer Martin J S, Walter Harriet S

机构信息

The Ernest and Helen Scott Haematological Research Institute, Leicester Cancer Research Centre, University of Leicester, Leicester, UK.

Respiratory Sciences, University of Leicester, Glenfield Hospital, Leicester, UK.

出版信息

Br J Haematol. 2025 May;206(5):1350-1354. doi: 10.1111/bjh.20033. Epub 2025 Mar 3.

DOI:10.1111/bjh.20033

PMID:40032583

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12078854/

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.

摘要

尽管CD20×CD3双特异性抗体（BsAbs）已在弥漫性大B细胞淋巴瘤（DLBCL）中显示出变革性活性，但一些患者无反应，另一些患者则复发。为了开始探索可能的局限性，我们比较了四种CD20×CD3生物类似BsAbs对四种CD20表达范围相差100倍的DLBCL细胞系的体外活性。所有四种生物类似BsAbs均显示出优于利妥昔单抗的体外活性，其中生物类似物格菲妥单抗始终是最有效的。此外，在低水平CD20表达的情况下，生物类似物格菲妥单抗和奥多妥单抗仍保留显著活性。最后，一种DLBCL细胞系尽管诱导了显著的T细胞和NK细胞活化，但对所有四种CD20×CD3 BsAbs均表现出内在抗性。