Ther A B CD 2

ownloade short circulating half-life and side effects of IFNα affect its dosing schedule and efficacy. Fusion of IFNα mor-targeting monoclonal antibody (MAb-IFNα) can enhance potency due to increased tumor localiand improved pharmacokinetics. We report the generation and characterization of the first bispecific FNα, designated 20-C2-2b, which comprises two copies of IFNα2b and a stabilized F(ab)2 of hL243 nized anti–HLA-DR; IMMU-114) site-specifically linked to veltuzumab (humanized anti-CD20). In vitro, 2b inhibited each of four lymphoma and eight myeloma cell lines, and was more effective than monoc CD20-targeted MAb-IFNα or a mixture comprising the parental antibodies and IFNα in all but one DR/CD20) myeloma line, suggesting that 20-C2-2b should be useful in the treatment of various opoietic malignancies. 20-C2-2b displayed greater cytotoxicity against KMS12-BM (CD20/HLA-DR ma) compared with monospecific MAb-IFNα, which targets only HLA-DR or CD20, indicating that all components in 20-C2-2b could contribute to toxicity. Our findings indicate that a given cell's responthree siveness to MAb-IFNα depends on its sensitivity to IFNα and the specific antibodies, as well as the expression and density of the targeted antigens. Cancer Res; 70(19); 7600–9. ©2010 AACR.