Document Type
Article
Publication Date
10-24-2022
Identifier
DOI: 10.3389/fmed.2022.1034594; PMCID: PMC9637670
Abstract
Diffuse large B-cell lymphoma (DLBCL), the most common form of lymphoma, is typically treated with chemotherapy combined with the immunotherapy rituximab, an antibody targeting the B cell receptor, CD20. Despite the success of this treatment regimen, approximately a third of DLBCL patients experience either relapse or have refractory disease that is resistant to rituximab, indicating the need for alternative therapeutic strategies. Here, we identified that CD74 and IL4R are expressed on the cell surface of both CD20 positive and CD20 negative B cell populations. Moreover, genes encoding CD74 and IL4R are expressed in lymphoma biopsies isolated from all stages of disease. We engineered bispecific antibodies targeting CD74 or IL4R in combination with rituximab anti-CD20 (anti-CD74/anti-CD20 and anti-IL4R/anti-CD20). Bispecific antibody function was evaluated by measuring direct induction of apoptosis, antibody-dependent cellular phagocytosis (ADCP), and antibody-dependent cellular cytotoxicity in both rituximab-sensitive and rituximab-resistant DLBCL cell lines. Both anti-CD74/anti-CD20 and anti-IL4R/anti-CD20 were able to mediate ADCC and ADCP, but CD74-targeting therapeutic antibodies could also mediate direct cytotoxicity. Overall, this study strongly indicates that development of bispecific antibodies that target multiple B cell receptors expressed by lymphoma could provide improved defense against relapse and rituximab resistance.
Journal Title
Front Med (Lausanne)
Volume
9
First Page
1034594
Last Page
1034594
Keywords
CD20; CD74; IL4R; bispecific antibody; cancer therapy; diffuse large B cell lymphoma; lymphoma; rituximab
Recommended Citation
Geanes ES, Krepel SA, McLennan R, Pierce S, Khanal S, Bradley T. Development of combinatorial antibody therapies for diffuse large B cell lymphoma. Front Med (Lausanne). 2022;9:1034594. Published 2022 Oct 24. doi:10.3389/fmed.2022.1034594
Comments
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Publisher's Link: https://www.frontiersin.org/articles/10.3389/fmed.2022.1034594/full