Since tumors are often infiltrated by macrophages, it would be advantageous to turn these types of cells into cytotoxic effector cells. Here, we have designed a novel bispecific antibody (BsAb) that targets both tumor antigen (CD20) and the FcαRI receptor (CD89). This antibody could be used to lyse tumors by connecting tumor cells to CD89-expressing immune effector cells such as macrophages and neutrophils. Previously there were very limited attempts to exploit FcαRI-expressing cells as effector cells for tumor cell-killing, largely due to the lack of an appropriate in vivo model, since mice do not express a human CD89 homolog. In this study, we used a transgenic mouse strain with specific expression of CD89 on macrophages and monocytes. In this transgenic mouse model, the CD89 bispecific antibody showed significant anti-tumor activities, demonstrating that bispecific antibodies can redirect macrophages, including M2 macrophages, to mediate additional effector function in the tumor microenvironment. This approach realized the full potential of the innate immune system and could be applied to other tumor-associated antigens especially the solid tumors, thus has potential to translate into clinical benefits in human cancers.
Keywords: ADCC; CD20; CD89; FcαRI; bispecific antibody.