Follicular Lymphoma 1 (FL1)

Target: B-cell
Action: promotes lysis
FDA: Ofatumumab binds specifically to both the small and large extracellular loops of the CD20402 molecule. The CD20 molecule is expressed on normal B lymphocytes (pre-B- to mature403 B-lymphocyte) and on B-cell CLL. The CD20 molecule is not shed from the cell surface and is404 not internalized following antibody binding.405406 The Fab domain of ofatumumab binds to the CD20 molecule and the Fc domain mediates407 immune effector functions to result in B-cell lysis in vitro. Data suggest that possible408 mechanisms of cell lysis include complement-dependent cytotoxicity and antibody-dependent,409 cell-mediated cytotoxicity.

Target: CD20 antigen --> Y-90
Action: beta emission causes damage
FDA: Ibritumomab tiuxetan binds specifically to the CD20 antigen (human B-lymphocyte-restricted differentiation antigen,Bp35). The apparent affinity (KD) of ibritumomab tiuxetan for the CD20 antigen ranges between approximately 14 to18 nM. The CD20 antigen is expressed on pre-B and mature B lymphocytes and on > 90% of B-cell non-Hodgkin’slymphomas (NHL). The CD20 antigen is not shed from the cell surface and does not internalize upon antibody binding.The chelate tiuxetan, which tightly binds Y-90, is covalently linked to ibritumomab. The beta emission from Y-90induces cellular damage by the formation of free radicals in the target and neighboring cells.Ibritumomab tiuxetan binding was observed in vitro on lymphoid cells of the bone marrow, lymph node, thymus, red andwhite pulp of the spleen, and lymphoid follicles of the tonsil, as well as lymphoid nodules of other organs such as thelarge and small intestines.