Integrin β7 (active-conformer epitope recognized by the MMG49 antibody)

Class

Autologous CAR-T cell therapy

Pathway

CAR construct built from the MMG49 monoclonal antibody, which recognizes an activated conformational epitope of integrin β7 selectively expressed on multiple myeloma cells; in-licensed by Otsuka from Osaka University

Integrin β7 is a cell-surface adhesion protein that pairs with a partner subunit (α4 or αE) to form a receptor governing how cells attach to their surroundings and migrate, particularly in mucosal and lymphoid tissues. Integrins exist in an inactive, low-affinity shape and an activated, high-affinity shape; this mechanism exploits an antibody that recognizes only the activated conformation of integrin β7, which is disproportionately displayed on malignant plasma cells in multiple myeloma compared with most normal tissue. That antibody's antigen-binding domain is engineered into a chimeric antigen receptor (CAR) and introduced into a patient's own T cells, redirecting them to recognize and destroy cells bearing this activated epitope. The biological rationale for restricting recognition to the active conformer, rather than total integrin β7, is to sharpen tumor selectivity: because resting normal cells largely display the inactive form, targeting the activated shape aims to reduce engagement of healthy tissue while still capturing myeloma cells that constitutively express the activated receptor. This class of therapy is relevant in multiple myeloma, a plasma cell cancer, and reflects a broader strategy of using conformation-specific rather than expression-level-specific antigens to improve the selectivity of cell-based immunotherapies.