The disclosure provides a tetra-specific antibody monomer having a N-terminal and a C-terminal, comprising in tandem from the N-terminal to the C-terminal, a first scFv domain at the N-terminal, a second scFv domain, a Fab domain, a Fc domain, and a third scFv at the C-terminal, wherein the first scFv domain, the second scFv domain, the Fab domain, and the third scFv domain each has a binding specificity against a different antigen. In one embodiment, the antigen is a tumor antigen, an immune signaling antigen, or a combination thereof. In one embodiment, the antigen includes CD19, CD3, CD137, 4-1BB, and PD-L1. Multi-specific antibodies comprising the disclosed tetra-specific antibodies are also provided.
