Generation of anti-bovine CD20 monoclonal antibody with cytotoxic activity for the depletion of bovine B-cell lymphoma cells

Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis (EBL), which manifests as B-cell lymphomas in cattle. However, the effective therapy for EBL has not yet been developed. While the usage of anti-human CD20 monoclonal antibody (mAb) for B-cell depletion therapy (BCDT) can provide remarkable curative effects on several types of B-cell tumors in humans, this approach remains problematic in cattle due to the lack of anti-bovine CD20 (boCD20) mAb for BCDT. Here, we show that newly developed mAb targeting boCD20 utilizes effector function to deplete EBL-driven B-cell lymphoma cells and bovine B cells. Anti-boCD20 mAb not only specifically recognized boCD20 but also exhibited the cytotoxic function against EBL-derived B-cell lymphoma cells and bovine B cells mediated through Ab-dependent cell-mediated cytotoxicity (ADCC) and complement-mediated cytotoxicity (CDC) as well as direct cell death. Furthermore, the treatment of immunodeficient mice transplanted with EBL-derived B-cell lymphoma cells with anti-boCD20 mAb led to inhibition of their growth. Thus, our findings highlight boCD20 as a valid marker for identifying B cells and EBL-derived B-cell lymphoma cells in cattle and provide support for boCD20 as a potential target for mAb-mediated depletion for the therapy of EBL.