Unleashing MEDI2228: A Potent BCMA-Targeted ADC for Multiple Myeloma Therapy

A novel antibody-drug conjugate (ADC) called MEDI2228 has been developed to target the B-cell maturation antigen (BCMA), a protein found in multiple myeloma (MM) cells. The drug is designed to specifically bind to BCMA and deliver a DNA cross-linking pyrrolobenzodiazepine (PBD) to cancer cells, inducing apoptosis. MEDI2228 has shown to be highly effective in vitro against 80% of MM cell lines tested, regardless of BCMA expression levels, and is also active against cells resistant to other therapies. In animal models, a single dose of MEDI2228 resulted in tumor regression.

Serum levels of soluble BCMA (sBCMA), which can interfere with antibody-based treatments, were found to be higher in MM patients than in healthy individuals. MEDI2228 was engineered to have a weaker binding affinity to sBCMA and a stronger binding to membrane-bound BCMA, maintaining its cytotoxicity even in the presence of high sBCMA levels.

Furthermore, MEDI2228 was shown to target and eliminate CD19+CD138- clonogenic cells, a population of cells in the bone marrow of MM patients that can contribute to disease progression. This suggests that MEDI2228 has the potential to target both the main MM cells and the stem-like cells, which could lead to a more sustained clinical response in MM, a disease characterized by genetic heterogeneity.