Harnessing the Power of DuoBody-CD3xCD20: A Comprehensive Overview of Its Potent Anti-Tumor Activity and Clinical Evaluation in B-Cell Malignancies

3 June 2024
DuoBody-CD3xCD20, a full-length bispecific IgG1 antibody, was developed using controlled Fab-arm exchange technology and features a modified Fc region. It has been shown to activate and proliferate CD4+ and CD8+ T cells, leading to cytotoxic activity against CD20-positive cells, as evidenced by flow cytometry and BrdU incorporation assays. The CD20-specific Fab arm, based on the 7D8 antibody, was compared with other CD3 bsAbs targeting different B-cell antigens, revealing superior cytotoxic activity for the 7D8-based bsAb. In vivo studies in humanized mice confirmed the anti-tumor efficacy of DuoBody-CD3xCD20 in both prophylactic and therapeutic settings.

Non-clinical safety studies in cynomolgus monkeys indicated that DuoBody-CD3xCD20 induced significant and long-lasting B-cell depletion, which was reversible and correlated with the treatment dose. The pharmacokinetic profile showed similar bioavailability for subcutaneous and intravenous administration, with lower plasma cytokine levels observed after subcutaneous administration.

Genmab has initiated a First-in-Human clinical trial to assess the safety and preliminary efficacy of DuoBody-CD3xCD20 in patients with B-cell malignancies via subcutaneous administration, with enrollment currently ongoing. Disclosures indicate various affiliations and interests of the authors with Genmab and other entities.

How to Use Synapse Database to Search and Analyze Translational Medicine Data?

The transational medicine section of the Synapse database supports searches based on fields such as drug, target, and indication, covering the T0-T3 stages of translation. Additionally, it offers a historical conference search function as well as filtering options, view modes, translation services, and highlights summaries, providing you with a unique search experience.

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Taking obesity as an example, select "obesity" under the indication category and click search to enter the Translational Medicine results list page. By clicking on the title, you can directly navigate to the original page.

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By clicking the analysis button, you can observe that GLP-1R treatment for obesity has gained significant attention over the past three years, with preclinical research still ongoing in 2023. Additionally, there are emerging potential targets, such as GDF15, among others.

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Click on the image below to go directly to the Translational Medicine search interface.

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