In humans, passive immunotherapy with anti-CD20 monoclonal antibodies (mAbs) has created immeasurable improvements in outcomes of patients with B-cell malignancies. However, the lack of comparable reagents has precluded development of this approach in dogs. We developed a novel anti-canine CD20 mAb designated as 6C8. 6C8 recognized the extracellular domain of canine CD20 and showed high-affinity binding to canine CD20 in solution, as well as in its native conformation on canine B-cells. The 6C8 target was expressed invariably in B-cell lineage cells, but not in T-cells or myeloid cells. 6C8 promoted phagocytosis of B-cell lymphoma cells by macrophages, but in its current framework, it did not induce direct cytotoxicity or complement dependent cytotoxicity. In summary, we have established a novel anti-canine CD20 mAb that is useful as a diagnostic tool to phenotype B-cells, and which could be integrated as a tool for passive immunotherapy to treat dogs with B-cell disorders.
Bibliographical noteFunding Information:
We thank Catherine Smith for antibody development and Regis Krah for assistance with protein expression constructs. This work was supported by a MAF First Award Grant D12CA-302 (D.I.), Morris Animal Foundation D13CA-033 (J.F.M. and D.I.), Skippy Frank Fund for Life Sciences and Translational Research (D.I. and J.F.M.), NIH grant P30CA077598 (NCI Core Support Grant for the Masonic Cancer Center), Masonic Cancer Center Hematologic Malignancy Innovations Award and University of Minnesota Animal Cancer Care and Research Program.
- B-cell lymphoma
- Monoclonal antibody