MEDI2228

MEDI2228 is an antibody-drug conjugate (ADC) designed to target B-cell maturation antigen (BCMA), a protein highly expressed on malignant plasma cells in multiple myeloma. It consists of a fully human monoclonal antibody directed against BCMA, site-specifically conjugated via a protease-cleavable valine-alanine dipeptide linker to the cytotoxic pyrrolobenzodiazepine (PBD) dimer payload, tesirine[1][2][7]. Upon binding to membrane-bound BCMA on myeloma cells, the ADC is internalized and releases the PBD toxin intracellularly, causing DNA cross-linking and cell death. In addition to direct cytotoxicity, MEDI2228 induces DNA damage response pathways that enhance immune-mediated killing by upregulating interferon-stimulated genes and increasing CD38 expression on myeloma cells[5][6]. This immunomodulatory effect can sensitize tumor cells to other therapies such as daratumumab. Developed for relapsed/refractory multiple myeloma (RRMM), clinical trials have shown efficacy but also notable toxicity related to its PBD payload[3][4].