Humoral Immune-Oncology (HIO) mechanisms utilize antibodies as well as immune-effector cells to kill dysregulated cancer cells. Some tumor cells produce immunosuppressive factors (HIO factors) that reduce HIO activity of therapeutic antibodies such as Rituxan® and Herceptin. Our Block-Removed Immunoglobulin Technology (BRITE) and HIO screening platforms allowed us to develop a unique pipeline of HIO factor-refractory therapeutic agents, HIO factor antagonist, or activator of immune cells including NK cells.