administering the therapeutic agent targeting CD3 to a genetically-modified, non-human mammal whose genome comprises a replacement of a nucleic acid sequence encoding all or a portion of the extracellular region of an endogenous CD3e with a nucleic acid sequence encoding the corresponding region of a human CD3e, wherein the replacement results in a sequence encoding a chimeric CD3e comprising an amino acid sequence that is at least 95% identical to amino acids 1-126 of SEQ ID NO: 7, wherein the chimeric CD3e associates with endogenous CD3γ and endogenous CD3δ, forming a functional CD3 complex on T cells in the mammal, wherein the non-human mammal detectably expresses the chimeric CD3e on the surface of one or more T cells, wherein the mammal has a cancer; and

determining the inhibitory effects of the therapeutic agent to the cancer.