Mesothelin (MSLN) x CD47 (bispecific)

Class

CD47 x Mesothelin bispecific antibody

Pathway

Tumor-restricted CD47 ('don't eat me' signal) blockade on MSLN-positive tumor cells, promoting macrophage-mediated phagocytosis while sparing healthy tissue

Mesothelin (MSLN) is a cell-surface protein anchored to the outer membrane of cells lining certain body cavities; it is expressed at very low levels on normal tissue but is markedly overexpressed on several solid tumors, including mesothelioma and cancers of the ovary and pancreas. CD47 is a distinct surface protein present on nearly all healthy cells that functions as a 'don't eat me' signal: by engaging the receptor SIRPα on macrophages, it restrains these innate immune cells from engulfing (phagocytosing) the cell that displays it. Tumor cells frequently exploit this signal to evade immune clearance. Blocking CD47 broadly would remove this restraint everywhere in the body, including on blood cells that also depend on it for survival, creating a risk of anemia and low platelet counts. A bispecific antibody that binds both MSLN and CD47 is designed to concentrate CD47 blockade on cells that also display MSLN, largely tumor cells, while leaving CD47 largely undisturbed on healthy tissue lacking MSLN. The intended result is that macrophages are selectively licensed to engulf and clear tumor cells, a mechanism relevant across mesothelin-expressing solid tumors where boosting innate immune clearance is a therapeutic goal.