Targeting BCMA with MEDI2228: A Promising Antibody-Drug Conjugate for Multiple Myeloma Therapy

3 June 2024
Despite significant improvements in treatment, multiple myeloma (MM) is still incurable. The B-cell maturation antigen (BCMA) is a promising target for MM therapies due to its limited presence in normal plasma cells and widespread presence in myeloma cells. MEDI2228 is a new antibody-drug conjugate (ADC) that targets BCMA, consisting of a human antibody linked to a DNA cross-linking pyrrolobenzodiazepine (PBD) dimer through a cleavable linker. MEDI2228 is quickly internalized and directed to lysosomes, where it induces DNA damage and cell death. It showed high efficacy in 80% of MM cell lines tested, regardless of BCMA expression levels, and was effective against resistant cell models and in the presence of bone marrow stromal cells. In animal models, a single dose of MEDI2228 led to tumor shrinkage.

Serum levels of soluble BCMA (sBCMA) are higher in MM patients, which could interfere with antibody therapies. MEDI2228's antibody was selected for its low binding to sBCMA and high binding to membrane-bound BCMA, maintaining its cytotoxicity even with high levels of sBCMA present. Additionally, MEDI2228 can target and eliminate CD19+CD138- clonogenic cells found in the bone marrow of MM patients, which are similar to MM plasma cells and express BCMA. MEDI2228's ability to target both bulk plasma cells and quiescent clonogenic cells suggests it may provide a more enduring clinical response for MM, a genetically diverse disease. The disclosures indicate various affiliations with MedImmune and other pharmaceutical entities for several authors.

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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