daratumumab and hyaluronidase-fihj

A co-formulation composed of daratumumab, a human immunoglobulin (Ig) G1 kappa monoclonal antibody directed against the cell surface glycoprotein cluster of differentiation 38 (CD-38; CD38), and a recombinant form of human hyaluronidase (rHuPH20), with potential antineoplastic activity. Upon subcutaneous administration of daratumumab and hyaluronidase-fihj, daratumumab targets and binds to CD38 on certain CD38-expressing tumors, such as multiple myeloma (MM) and plasma cell leukemia. This binding induces direct apoptosis through Fc-mediated cross-linking and triggers immune-mediated tumor cell lysis through antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP) immune responses. CD38, a transmembrane glycoprotein, is expressed in both hematopoietic and non-hematopoietic lineage cells. Hyaluronidase-fihj hydrolyzes and degrades the glycosaminoglycan hyaluronic acid (HA), thereby decreasing interstitial viscosity and enhancing penetration of daratumumab through the interstitial space. This facilitates the delivery of daratumumab to CD38-expressing tumor cells.