Anti-Human CD19 (Tafasitamab) (LT3100-GRP)

CD19 is a B cell surface glycoprotein that enhances B cell receptor signaling and tumor cell proliferation 1. CD19 is an attractive immunotherapy target for cancers of lymphoid origin due to its early and persistent expression throughout B cell maturation 2. Tafasitamab is a humanized anti-CD19 monoclonal antibody developed by MorphoSys AG under a license from Xencor for the treatment of B cell malignancies 1. The chimeric antibody was engineered by combining the variable region genes of mouse anti-CD19 antibody (clone 4G7) with human light chain κ and heavy chain constant regions 1,2. Light and heavy chain constructs were co-transfected into 293E cells and antibodies were purified using protein A chromatography 2. Additionally, the Fv of 4G7 was humanized, affinity-matured using library design automation, and substitutions S239D/I332E were introduced to increase Fcγ receptor affinity to human 2, mouse 2, and cynomolgus monkey 3 FcγRs, with FcγRIIIa affinity being particularly enhanced 2. Tafasitamab mediates B cell lysis via apoptosis and immune effector mechanisms including antibody-dependent cellular cytotoxicity (ADCC) 2,4 and antibody-dependent cellular phagocytosis 2. Tafasitamab also increases antiproliferative activity and inhibits lymphoma growth in mouse xenograft models. ADCC is mediated by natural killer cells 5 through a granzyme B-dependent mechanism that is further enhanced by lenalidomide 6,7. Tafasitamab is also known as XmAb5574 1.