This invention describes a novel format of monomeric bispecific fusion protein with immune activating property for clinical therapies. A bispecific fusion protein includes a first targeting domain with a specificity for a first target of interest a bridging domain derived from a constant region of a light chain or heavy chain of an immunoglobulin, which may be a human immunoglobulin and a second targeting domain with a specificity for a second target of interest. The bispecific fusion protein may further include a linker fused to the N-terminus or the C-terminus of the bridging domain. The first targeting domain is fused to the bridging domain and the second targeting domain is fused to the bridging domain or the linker. The linker may include a GGGGS sequence. The first target of interest may be CD20, Her2/neu, or EpCAM, and the second targeting domain is a T-lymphocyte activating domain.
